Oral data collecting device for diagnosis or prognosis

ABSTRACT

An apparatus that monitors information associated with an oral cavity is provided, the apparatus comprising: a three-dimensional oral appliance; a data collection device having at least one sensor and/or hydrogel like material configured to sense the information associated with the oral cavity; an interface device cooperatively coupled to the data collection device, the interface device configured to transfer the information from the sensor device to a receiving device external to the oral cavity or the entire device is analyzed.

BACKGROUND

Oral appliances that allow drug delivery to the oral cavity have beendeveloped that have a reservoir to hold liquid medicaments or a cargoarea that have a foam disposed in the cargo area for delivery of thedrug to the oral cavity. These oral appliances are available inuniversal sizes to generically fit adults or are custom made for aprecise fit to the teeth and gums of the individual patient.

Oral appliances that are provided in universal sizes often do notadequately match the patient's actual oral cavity characteristics. Thiscan lead to poor contact in areas where such oral appliances are adaptedto deliver the drug. Custom made oral appliances present a better fit tothe patient's oral cavity since they are fabricated to match the actualoral cavity in which they are employed.

Based on the above, new oral appliances are needed that improvemeasurement of the biological activity occurring in the oral cavity, forexample, saliva activity, pressure, oxygen content, temperature, pH,bacteriologic/viral/cellular assays, gingival/periodontal fluids andexudates or other bodily fluids or exudates such as phlegm or sputum orother parameters in order to more accurately treat diseases on anindividual basis. Such oral appliances may be easily manufactured and,in some embodiments, based on the patient's actual oral cavityarchitecture so that they are easy and comfortable for the patient towear, or the oral appliance can be a universal fit appliance for theperson to wear.

SUMMARY

New oral appliances are provided that apply sensors to an oral cavity ina three dimensional manner. In various embodiments an oral appliance isprovided for sensing various biological characteristics includingtemperature, pH, O₂, and CO₂, content in saliva or sulcular assays orother conditions in the mouth.

The oral appliance contains an interior surface having a sensor arraydisposed in or on at least a portion of and/or the entire interiorsurface of the oral appliance. In some embodiments, the oral appliancecan be a universal oral appliance to fit most users. In someembodiments, the oral appliance is a custom fit oral appliance where theinterior surface of the oral cavity is formed to fit contours of atleast the portion of the teeth and/or soft tissue areas inside the oralcavity and is configured for supporting and holding the sensor array incontact with at least the portion of the teeth and/or soft tissue areasinside the oral cavity to assay the environment. In various embodiments,the oral appliance is monolithic or a single piece and the interiorsurface is individually custom fit and formed to fit contours of theteeth and/or soft tissue areas inside the oral cavity of a specificperson and no other. Unlike prior art oral appliances, an embodiment ofthe oral appliance of the present application has differing types ofsensor arrays as part of the appliance. In certain embodiments, the oralappliance comprises several variations configured to assay varioussubstances.

In some embodiments, the sensors can be at discrete positions on theexterior surface of the oral appliance, and/or on the interior surfaceof the oral appliance to sense the biological environment within theoral cavity and transmit the data to a remote computer of the user,and/or health care provider to monitor, diagnose or prognose thecondition of the wearer's oral cavity over a continuous period of time(e.g., minutes, hours, 24 hours, 48 hours, 1 week).

In certain embodiments, the material of the oral appliance is a polymergel, a hydrogel, a brush polymer or a combination thereof, or of somesponge like character or tampon material. In some embodiments, thehydrogel comprises, consists essentially of or consists of an amountfrom about 10% to about 90% by weight, from about 20% to about 80% byweight, from about 30% to about 70% by weight, from about 40% to about60% by weight of the oral appliance. The material employed serves toabsorb cells, chemical secretions, and other biomaterials. Once the oralappliance has been used for a period of time to allow sampling of cells,chemical secretions, and other biomaterials, the user removes theappliance and it is then analyzed.

In some embodiments, the oral appliance is optionally constructed from adigital data set representing at least a portion of or all of the teethand/or soft tissue areas inside the oral cavity. This permits preciseplacement of sensors at positions of interest.

In some embodiments, there is an oral appliance for assaying chemicalproperties or environmental conditions at a portion of teeth and/or softtissue areas inside an oral cavity, the oral appliance comprising aninterior surface having a sensor array disposed in or on at least aportion of and/or all of the interior surface of the oral appliance, theinterior surface being formed to fit contours of at least the portion ofthe teeth and/or soft tissue areas inside the oral cavity and beingconfigured for holding the sensor array in contact with at least theportion of the teeth and/or soft tissue areas inside the oral cavity topermit measurement of the aforesaid chemical and/or environmentalproperties within the oral cavity.

In some embodiments, there is an oral appliance for improving assays ofsaliva collection. Presently, assays of saliva utilize a single “spit intime” which is limited in quality and quantity since the assays onlymeasure a moment. A person can be dehydrated, have just eaten or is onmedications which dry the mouth, all of which affect the quality andquantity of the saliva. Sputum and phlegm tests which measure infectionsin the breathing passages including the sinuses can be assayed with thisoral appliance embodiment.

In some embodiments, there is a computer implemented method of making anoral appliance, the method comprising: creating a digital record of apatient's oral cavity which is called the Base Image (BI). The BI can beobtained by the conventional analog method of taking an impression ofthe patient's mouth with common impression materials such as alginate,polyvinyls, silicones or other such materials or may be taken withvarious scanning devices for a more direct digital record of thetopography of the patient's mouth. With the analog method, either theimpression would be poured with dental stone and the positive modelwould be scanned or the impression itself, the negative, would bescanned yielding a digital record of the BI.

The BI is a permanent record of the topography of the patient's mouthand is digitally stored to provide a base record and also for futuredigital manipulations to form oral appliances. Computerized programmanipulations are made to create the first digital image (Dig1) of atleast a portion of the teeth, and/or soft tissue of the oral cavity.Dig1 is an additive process in which programmatically a platformappliance image is digitally layered over the BI. Dig1 is the platformcarrier for placing sensors at discrete positions in the mouth or asensor web in the mouth. A second subtractive process of the BI isprogrammatically made and this image is stored as the second digitalimage (Dig2). Dig2 is a three dimensional representation of thegeographic area to have the sensors disposed in the oral appliance. Thesecond digital image (Dig2) is a subtractive process made throughprogram manipulations where spaces in the oral appliance are generatedto dispose the sensors against at least a portion of the teeth and/orsoft tissue of the oral cavity; the second digital image is subtractedfrom the corresponding area of the first digital image (Dig1) whichforms a final third digital image (Dig3) of the oral appliance withindentations formed by the second digital image Dig 2 and into whichsensors are disposed at an area of interest. It is from this thirddigital image that the appliance is manufactured and made virtuallythrough the computer.

In some embodiments, the BI is a permanent record of the topography ofthe patient's mouth and is digitally stored to provide a base record andalso for future digital manipulations to form oral appliances.Computerized program manipulations are made to create the first digitalimage (Dig1) of at least a portion of the teeth, and/or soft tissue ofthe oral cavity. Dig1 is an additive process in which programmatically aplatform appliance image is digitally layered over the BI. Dig1 is theplatform carrier for placing sensors at discrete positions in the mouthor a sensor web in the mouth. A second additive process of the BI isprogrammatically made and this image is stored as the second digitalimage (Dig2). Dig2 is a three dimensional representation of thegeographic area to have the sensors disposed in the oral appliance. Thesecond digital image (Dig2) is an additive process made through programmanipulations where spaces in the oral appliance are generated todispose the sensors against at least a portion of the teeth and/or softtissue of the oral cavity; the second digital image is added to thecorresponding area of the first digital image (Dig1) which forms a finalthird digital image (Dig3) of the oral appliance with indentationsformed by the second digital image Dig. 2 and into which sensors aredisposed at an area of interest. It is from this third digital imagethat the appliance is manufactured and made virtually through thecomputer.

In some embodiments, there is a network based computer system for makingan oral appliance pre-loaded with at least one sensor in at least onelocation. The network based computer system includes programming (eitherin the form of software, firmware, or hardware) for generating Dig1 datarepresenting an additive overlay of at least a portion of the teethand/or soft tissue areas of the oral cavity of a patient built upon theBI. The BI data then has one or more surface areas identified by atechnician or doctor using the computer system to perform digitalsegmentation of at least a portion of the teeth and/or soft tissue areasof the oral cavity to identify areas of interest for sampling bysensors. Essentially, the original image of the mouth (BI) provides thetemplate for creating the additive first digital image (Dig1) and thesegmented second digital image (Dig2) through various programmanipulations of the base image of the mouth (BI) to form a finalshowing the positions of the sensors in the third digital image of themouth (Dig3) from which image the appliance will be fabricated.

In some embodiments, there is a computer readable storage medium storinginstructions that, when executed by a computer, cause the computer to:receive BI data from an imaging device, from which image an additivemanipulation is performed yielding the Dig1 data representing theplatform carrier over at least a portion of the teeth and/or softtissues areas of the oral cavity of a patient. The BI is then againmanipulated by identifying at least one surface area thereof to generatea Dig2 data which represents indentations to be made in the interiorsurface of the Dig1 layered structure for acceptance of a sensor ormultiple sensors at areas of interest. A merging of the Dig1 data withthe additive or subtractive Dig2 manipulation forms the Dig3 data fromwhich the oral appliance can be produced, wherein the Dig3 datacomprises positions for at least one sensor to be placed in the oralcavity areas of interest.

In some embodiments, there is an oral appliance for collecting a samplefrom at least a portion of teeth and/or soft tissue areas inside an oralcavity, the oral appliance comprising an interior surface having anabsorptive material disposed in or on at least a portion of and/or allof the interior surface of the oral appliance, the interior surfacebeing formed to fit contours of at least the portion of the teeth and/orsoft tissue areas inside the oral cavity and being configured forholding the absorptive material in contact with at least the portion ofthe teeth and/or soft tissue areas inside the oral cavity to collect thesample therefrom. The absorptive material follows surface areas of themouth to be tested and is disposed in layers defined by the Dig2manipulation of the BI and added to the Dig1 layer structure.

Briefly stated, a further embodiment provides a computer implementedmethod and computer system for producing an oral appliance includingscanning an oral cavity to produce a three dimensional digitalrepresentation of an oral topography followed by presenting a display ofthe scan. The system accepts input indicating areas of interest to besampled by sensors. A first 3D digital representation of a platformcarrier based on the scan is created. A user inputs a sensor type to beemployed and the system calculates an indentation size (area and depth)based on the sensor type and generates a second 3D digitalrepresentation of the indentation. The second 3D digital representationis subtracted from the first 3D digital representation to a form a third3D digital representation which is used to operate a 3D printer toproduce the oral appliance with the indentations for sensors.

In another embodiment, there is an apparatus that monitors informationassociated with an oral cavity, the apparatus comprising: athree-dimensional oral appliance; a data collection device having atleast one sensor configured to sense the information associated with theoral cavity; an interface device cooperatively coupled to the datacollection device, the interface device configured to transfer theinformation from the sensor device to a receiving device external to theoral cavity. In some embodiments, the information associated with theoral cavity comprises at least one of pH, temperature, pressure, O₂content, CO₂ content, bacterial content, or saliva quantity/quality orgingival/periodontal fluids and exudates or other bodily fluids orexudates such as phlegm or sputum.

In another embodiment, there is a computer-readable medium for making anoral appliance containing a discrete region for placing a sensor tocollect biological information about a patient's oral cavity, thecomputer-readable medium comprising instructions that, when executed bya processing device, cause the computer to: generate first digital datarepresenting at least a portion of teeth and/or soft tissue areas of theoral cavity of the patient, the first digital data generated from animaging device having a base image of the oral cavity; generate a seconddigital data from the base image by performing a digital segmentation ofat least a portion of the teeth and/or soft tissue areas of the oralcavity to determine the discrete region of the oral cavity to place thesensor; and combine the first digital data (Dig1) and the second digitaldata (Dig2) to form a third digital data (Dig3) from which an oralappliance can be produced into 3D printing data, wherein the thirddigital data comprises the discrete region for placing the sensor tocollect the biological information of the patient's oral cavity

In another embodiment, there is a computer-readable medium comprisinginstructions that, when executed by a processing device, performoperations comprising: monitoring information associated with an oralcavity from a data collection device of a three-dimensional oralappliance; the data collection device having at least one sensorconfigured to sense the information associated with the oral cavity; andan interface device cooperatively coupled to the data collection device,the interface device configured to transfer the information from thesensor device to a receiving device external to the oral cavity.

In another embodiment, there is an oral appliance for collectingbiological information about at least a portion of teeth and/or softtissue areas inside an oral cavity, the oral appliance comprising aninterior surface having a sampling medium disposed in or on at least aportion of and/or all of the interior surface of the oral appliance, theinterior surface being formed to fit contours of at least the portion ofthe teeth and/or soft tissue areas inside the oral cavity and beingconfigured for holding the sampling medium in contact with at least theportion of the teeth and/or soft tissue areas inside the oral cavity,the sampling medium configured to collect biological tissue from theoral cavity and be removed from the interior surface of the oralappliance. In some embodiments, the sampling medium is also configuredto collect biological fluids, exudates or cells.

Additional features and advantages of various embodiments will be setforth in part in the description that follows, and in part will beapparent from the description, or may be learned by practice of variousembodiments. The objectives and other advantages of various embodimentswill be realized and attained by means of the elements and combinationsparticularly pointed out in the description and appended claims.

The above, and other objects, features and advantages of the presentdisclosure will become apparent from the following description read inconjunction with the accompanying drawings, in which like referencenumerals designate the same elements.

The foregoing is a summary and thus contains, by necessity,simplifications, generalizations, and omissions of detail; consequently,those skilled in the art will appreciate that the summary isillustrative only and is not intended to be in any way limiting. Otheraspects, inventive features, and advantages of the present disclosure,as defined solely by the claims, will become apparent in thenon-limiting detailed description set forth below.

Furthermore, while various features and objects are presented in theabove summary, said summary is not intended to limit the appended claimsto coverage of embodiments which address any one, any combination, orall of the above noted features and objects.

BRIEF DESCRIPTION OF THE DRAWINGS

In part, other aspects, features, benefits and advantages of theembodiments will be apparent with regard to the following description,appended claims and accompanying drawings wherein:

FIG. 1 is a perspective view of an embodiment of an oral appliance forcovering upper teeth and/or soft tissues of a patient, the oralappliance being shown without teeth and/or soft tissues inserted in theoral appliance.

FIG. 2 is a front and right side elevation view of an embodiment of theoral appliance of FIG. 1 and a second oral appliance for covering lowerteeth and/or soft tissues, wherein locations of sensors (smallrectangles) are shown. In one embodiment, the sensors are situatedadjacent to a gingival sulcus region.

FIG. 3 illustrates a cross section of an embodiment of an oral applianceas a dental oral appliance having a sensor 36 disposed in an indentationdefined by a Dig2 image.

FIG. 4 illustrates an enlarged side cross sectional view of anembodiment of the oral appliance configured to correspond to and coverthe tooth and soft tissue areas inside the oral cavity.

FIG. 5 illustrates an embodiment of a virtual image (Dig2) of theregions along the sulcus (gumline) where a sensor or a plurality ofsensors are to be disposed at discrete or continuous regionscorresponding to areas of interest.

FIG. 5A illustrates an enlarged view of a virtual image (Dig2) of theregions along the sulcus (gumline) where sensors for taking measurementor hydrogel for sampling cells or other biological samples are disposed.

FIG. 5B illustrates an enlarged interior view of a virtual image (Dig1)of the oral appliance that is made by taking the BI of the oral cavityand creating a digital image that adds layers over the oral cavityincluding the teeth, gums, soft tissue areas and/or the palate, whereDig1 does not show locations corresponding to areas where the sensor isgoing to be disposed.

FIG. 5C illustrates an enlarged interior view of a virtual image (Dig3)of the oral appliance wherein the virtual image is a subtraction of theDig2 digital data from the BI data, from which the oral appliance isproduced that has regions along the sulcus (gumline) wherein a polymergel material for sampling or a sensor, sensor web, sensors, or an arrayof sensors are disposed.

FIG. 6A schematically shows an embodiment of an oral applianceconfigured for application to the lower teeth and gums and a cargo areahas a pressure sensor mounted either by hand or robotically on the outersurface of the oral appliance, which for example, can monitor pressureon a biting surface for teeth grinding (e.g., bruxism) or to assist inbite equilibration (adjusting one's bite).

FIG. 6B schematically shows an embodiment of an oral applianceconfigured for application to the lower teeth and gums and a cargo areathat has a hydrogel disposed either by hand or robotically on theinterior surface of the oral appliance, which for example, can collectcells, for example, from the sulcus for culture and sensitivity testing.The hydrogel can have a tab for easy removal of the hydrogel, or thewhole tray can then be sent to the lab for further testing.

FIG. 7 is a block diagram of an embodiment of a computer-implementedsystem for producing an oral appliance for measuring chemical, physical,and environmental parameters.

FIG. 8 is a flow chart illustrating an embodiment of thecomputer-implemented system for producing an oral appliance forperforming oral cavity chemical, physical, and environmentalmeasurements including cell or saliva sampling.

FIG. 9A is a flow chart illustrating an embodiment of thecomputer-implemented system to generate and manufacture an oralappliance and use of the oral appliance by a patient.

FIG. 9B is a flow chart illustrating an embodiment of thecomputer-implemented system to generate and manufacture an oralappliance and use of the oral appliance by a patient.

FIG. 10A is a cross-sectional view of an area of the oral appliance ofFIG. 1 taken along line IXa-IXa, at an area of interest housing a sensorthat monitors physical, chemical, biological, and/or environmentalinformation associated with the oral cavity at a sulcus area.

FIG. 10B is the cross-sectional view of an area of the carrier shell ofFIG. 1 taken along line IXb-IXb wherein a carrier shell and an area ofinterest housing the apparatus that monitors physical, chemical,biological, and/or environmental information associated with the oralcavity at a portion of the carrier shell adjacent a bottom portion of anupper molar area are depicted.

FIG. 10C is a top view of the oral appliance of FIG. 1 depicted in asimplified manner lacking intricate detail for simplicity of viewing,indicating various components of the apparatus that monitors physical,chemical, biological, and/or environmental information associated withthe oral cavity (dashed line outlined) disposed at the bottom ofpositions for alignment adjacent bottoms of top molars, sensorspositioned in indentations of the interior surface of the oral appliancefor measurements of properties adjacent teeth, and sensors positioned inindentations of the exterior surface of the oral appliance. For example,the data collection device 302 (e.g., sensor) can measure oxygen orcarbon dioxide content in the oral cavity to monitor conditions such as,for example, sleep apnea, where oxygen content will be low.

FIG. 10D is a top plan view of the oral appliance of FIG. 1 depicted ina simplified manner lacking intricate detail for simplicity of viewing,indicating various components of the apparatus that monitors physical,chemical, biological, and/or environmental information associated withthe oral cavity. In this view, a plurality of data collection devicesare disposed in the interior surface and exterior surface of the oralappliance.

FIG. 10E is a top plan view of the oral appliance of FIG. 1 depicted ina simplified manner lacking intricate detail for simplicity of viewing,indicating various components of the apparatus that monitors physical,chemical, biological, and/or environmental information associated withthe oral cavity. In this view, a sensor web is provided in the interiorof the device that allows contact with the teeth.

FIG. 1OF is a top plan view of the oral appliance of FIG. 1 depicted ina simplified manner lacking intricate detail for simplicity of viewing,indicating various components of the apparatus that monitors physical,chemical, biological, and/or environmental information associated withthe oral cavity. In this view, a plurality of data collection devicesare disposed in the interior surface and exterior surface of the oralappliance and there is an electroconductive polymer disposed throughoutthe interior of the oral appliance.

FIG. 11 is a diagram of a system in which the oral appliance is used tomonitor, collect, transfer, process, and store physical, chemical,biological, and/or environmental information obtained from the oralcavity.

FIG. 12 is a block diagram of an apparatus that monitors informationassociated with an oral cavity, the apparatus comprising an oralappliance, a data collection device, an interface device coupled to thedata collection device, a processing device and a power supply.

FIG. 13 is a flowchart of one embodiment of instructions for theapparatus that monitors information associated with an oral cavity.First, information is monitored using a data collection device (e.g.,sensor). The monitored information is processed and then the processedinformation is transferred external to the oral appliance. Theinformation is then received external to the oral appliance. Thereceived information is then compared to user parameters. If the userparameters have been exceeded (e.g., increase in pH or carbon dioxidecontent, decrease in moisture, etc.), then an audio/visual alert oralarm is issued. The processed information is then stored external tothe oral appliance.

FIG. 14 is a flowchart of another embodiment of the oral appliance.Information is sampled using a sampling medium. The sampling medium isthen removed from the oral appliance. The sampling medium is processedto obtain certain information. The information is processed external tothe oral appliance. The received information is then compared to theuser parameters of FIG. 13. If the user parameters have been exceeded(e.g., decrease in pH or oxygen content, decrease inelectroconductivity, etc.), then an audio/visual alert or alarm isissued. The information is then stored external to the oral appliance.

FIG. 15 is a block diagram showing at least a portion of an exemplarymachine in the form of a computing system that performs methodsaccording to one or more embodiments disclosed herein.

It is to be understood that the figures are not drawn to scale unless soindicated. Further, the relationship between objects in a figure may notbe to scale, and may in fact have a reverse relationship as to sizeunless so indicated. The figures are intended to bring understanding andclarity to the structure of each object shown, and thus, some featuresmay be exaggerated in order to illustrate a specific feature of astructure. Accordingly, the figures are not intended to limit the scopeand breadth of the appended claims.

DETAILED DESCRIPTION

With regard to the following description, it is to be understood bythose skilled in the art that unless a specific number of an introducedclaim element is recited in the claim, such claim element is not limitedto a certain number. For example, introduction of a claim element usingthe indefinite article “a” or “an” does not limit the claim to “one” ofthe element. Still further, the following appended claims can containusage of the introductory phrases “at least one” and “one or more” tointroduce claim elements. Such phrases are not considered to imply thatthe introduction of a claim element by the indefinite articles “a” or“an” limits any particular claim containing such introduced claimelement to coverage of devices or processes containing only one suchelement or containing more than one such element, even when the sameclaim includes the introductory phrases “one or more” or “at least one.”

It is to be further understood that claim terminology relating toelements A, B, and C recited as “one of A, B, and C” is intended tocover devices or processes having one or more of element A, or one ormore of element B, or one or more of element C, and does not require thepresence of three of such elements A, B, and C, nor exclude coverage ofdevices or processes including the presence of three of such elements A,B, and C. Likewise, recitation of “at least one of A, B, and C” is to begiven the same interpretation. On the other hand, if it is intended tolimit coverage of a claim to devices or processes including one of eachof a set of elements, the phraseology “one of each of A, B, and C” or“at least one of each of A, B, and C” is used.

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing quantities of ingredients,percentages or proportions of materials, reaction conditions, and othernumerical values used in the specification and claims, are to beunderstood as being modified in all instances by the term “about.”Accordingly, unless indicated to the contrary, the numerical parametersset forth in the following specification and attached claims areapproximations that may vary depending upon the desired propertiessought to be obtained by the embodiments of the present disclosure. Atthe very least, and not as an attempt to limit the application of thedoctrine of equivalents to the scope of the claims, each numericalparameter should at least be construed in light of the number ofreported significant digits and by applying ordinary roundingtechniques.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the disclosure are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Moreover, all ranges disclosed hereinare to be understood to encompass any and all subranges subsumedtherein. For example, a range of “1 to 10” includes any and allsubranges between (and including) the minimum value of 1 and the maximumvalue of 10, that is, any and all subranges having a minimum value ofequal to or greater than 1 and a maximum value of equal to or less than10, e.g., 5.5 to 10.

It is also to be further understood that the doctrine of claimdifferentiation is to be applied across an independent claim and itsdependents and is not intended to be applied across a plurality ofindependent claims. For example, term A in a first independent claim maybe interpreted to have the same scope as term B in second independentclaim, while if term A is in a first independent claim and term Bfurther defines term A in claim dependent from the first independentclaim, then term A must have a broader scope than term B. In otherwords, phrases that differ from one independent claim to anotherindependent claim, may be interpreted to have equal scope and read oncommon structure yet present the structure using different terminologyin order account for differing interpretation of phrase language.

Reference will now be made in detail to various embodiments of thepresent disclosure, examples of which are illustrated in theaccompanying drawings. While the embodiments of the present disclosurewill be described in conjunction with the illustrated embodiments, itwill be understood that they are not intended to limit the disclosure tothose embodiments. On the contrary, the disclosure is intended to coverall alternatives, modifications, and equivalents, which may be includedwithin the disclosure as defined by the appended claims.

Headings where presented below are not meant to limit the disclosure inany way; embodiments under any one heading may be used in conjunctionwith embodiments under any other heading.

Oral Appliance

New oral appliances are provided that can provide diagnostic informationderived from at least a portion of the teeth and/or soft tissues insidethe oral cavity in a three-dimensional way. One advantage of the oralappliance, in some embodiments, is that it may be custom made to fit aspecific patient. As used herein a “custom fit” oral appliance refers toan oral appliance prepared to correspond to at least a portion of theteeth or all of the teeth and soft oral tissues of a specific patient.Typically, the custom fit appliance is prepared by a dental careprofessional (e.g., dentist, oral surgeon, medical doctor, other healthcare professional, manufacturer, etc.). The custom fit oral appliancecan be made from an impression mold, or using an analog or digital imagecapturing device. In some embodiments, the oral appliance provided bythis disclosure can be a boil-and-bite prefabricated device or a stockoral appliance, which can be manipulated by the patient's fingers toshape it against the teeth and gums. This is not a custom oral appliancebut can be manipulated by the patient to fit their mouth. As opposed toconventional oral appliances, the appliances provided herein can containa sensor in a cargo area of the oral appliance that can be generated by3D printing.

In some embodiments, the oral appliances disclosed herein can beuniversal, disposable, monolithic devices, manufactured in onecontinuous step(s), pre-loaded with one or more data collection devices(e.g., sensors or hydrogels) in or on at least a portion of the interiorand/or exterior surfaces of the appliance, and can sense chemical,physical, and/or environmental parameters and/or collect biologicalmaterial three dimensionally. In some embodiments, the oral appliancecan be transparent. Still another advantage of the oral appliance isthat, in various embodiments, it can be easily manufactured and iscomfortable for the patient to use. Other advantages of the oralappliances include greater efficacy over conventional oral datacollection techniques based on two-dimensional systems, userconvenience, enhanced patient compliance, reduced temporal requirementsto detect conditions, ease of use, and enhanced pressure applied to thegums.

In one embodiment, there is an oral appliance for monitoring at least aportion of teeth and/or soft tissue areas inside an oral cavity, theoral appliance comprising an interior surface having an apparatusdisposed in or on at least a portion of and/or all of the interiorsurface of the oral appliance, the interior surface being formed to fitcontours of at least the portion of the teeth and/or soft tissue areasinside the oral cavity and being configured to hold a data collectiondevice associated with the apparatus in contact with at least theportion of the teeth and/or soft tissue areas inside the oral cavity tomonitor a diagnostic area therein.

The soft tissue of the inside of the mouth, includes but is not limitedto any soft tissue adjacent or between the teeth, including but notlimited to the papilla, tissue of the upper and lower dental arches,marginal gingiva, gingival sulcus, inter-dental gingiva, gingival gumstructure on lingual and buccal surfaces up to and including themuco-gingival junction and/or the palate and/or the floor of the mouth.In various embodiments, the soft tissue area includes the muco-buccalfolds, hard and soft palates, lining mucosa, the tongue and/or attachedgingival tissue. In various embodiments, the oral appliance receives oneor more teeth including one or more molars, premolars, incisors,cuspids, tooth implant, or combination or portions thereof. In otherembodiments, the one or more sensors and/or hydrogel contained in theoral appliance can be disposed anywhere in or on the interior orexterior surface of the oral appliance adjacent to the gum and/or othersoft tissue areas of the oral cavity including the front, back, andocclusal surfaces of one or more teeth.

Referring to FIG. 1, an enlarged side view of an embodiment of the oralappliance 10 is illustrated, which has an interior surface 12 and anexterior surface 14, both comprising a polymer that can, in someembodiments, be in gel or hydrogel form.

The interior surface 12 contacts one or more teeth and/or soft tissueareas of a patient. The interior surface 12 is custom fit to theindividual patient's mouth and configured to receive all or a portion ofthe teeth and/or soft tissue areas inside the mouth. In this view, theinterior surface contacts the teeth and soft tissue. Oral appliancesinclude, but are not limited to, oral trays, oral holders, oral covers,or the like that are designed to be placed within the oral cavity. Theinterior surface 12 and/or exterior surface 14 of the oral appliancecontain one or more sensors and/or hydrogel disposed in or on thepolymer and the one or more sensors and/or hydrogel can be disposedanywhere within or on the monolithic oral appliance. For example, theone or more sensors and/or hydrogel can be disposed at discretepositions adjacent to the diagnostic or prognostic areas or uniformlydisposed throughout the device. As the interior and/or exterior surfaceof the oral appliance contacts the oral cavity, the one or more sensorsand/or hydrogel come into contact with the desired detection site orpressure from the device contacting tissue or fluid at the detectionsite (e.g., gums, tissue, teeth, etc.).

In some embodiments, unlike orthodontic appliances, the one or moreembodiments of the oral appliance are not designed to move teeth.Therefore, a plurality of oral appliances will be configured to hold theteeth in the same position within the appliance. The teeth position willnot change. However, the one or more sensors and/or hydrogel disposed inor on the oral appliance will be in the same or different areas atdifferent stages of the detection regimen with a variety of oralappliances. Thus, kits containing a plurality of devices can be providedwith different detection stages from the data collection device (e.g.,sensor, sensors, sensor array, and/or sensor web). Suitable sensorsinclude, but are not limited to temperature sensors, pressure sensors,moisture sensors, light sensors, pH sensors, acceleration sensors, orlike. These sensors in some embodiments, collect measurements from thepatient's gums, teeth, saliva, and tongue, such as vital signs,respiratory measures, blood oxygen level, carbon dioxide levels, headmotion, saliva chemistry, gingival chemistry, for example.

FIG. 2 is an enlarged side view of an embodiment of an oral appliance.In this embodiment, the oral appliance is transparent and holds teeth 16and or gums, which are covered by the oral appliance. The oral applianceincludes a surface that contains one or more sensors and/or hydrogel aspart of the polymer that, in use, monitors physical, chemical,biological, and/or environmental information, and/or collects biologicalmaterial at or near the gingival sulcus 20.

FIG. 3 illustrates an enlarged cross-sectional view of the portion ofthe oral appliance 30 and its contact points surrounding a tooth 32 andan interior surface 34 having at least one or more sensors and/orhydrogel 36 which extends up and contacts the gingival sulcus region 38.It will be understood that the one or more sensors and/or hydrogel canbe disposed throughout the interior and/or exterior of the device thatcontacts oral tissue. In the embodiment shown in FIG. 3, the interior ofthe device has one or more sensors and/or hydrogel disposed at discreteregions of the interior surface of the device adjacent to the areas tobe detected (e.g., tooth and/or soft tissue areas).

FIG. 4 illustrates an enlarged side cross-sectional view of anembodiment of the oral appliance 40 showing an outline of a tooth 42.The oral appliance 40 has an exterior surface 44 and interior surface46. The interior surface of oral appliance 40 contains one or moresensors and/or hydrogel, which contacts tooth 42 up to gingival area 48.In the embodiment shown, the one or more sensors and/or hydrogel in thepolymer layer extend and contact the buccal surfaces of the teeth andsurrounding gingival tissue and over adjacent gingival tissue on alingual side of the teeth. In some embodiments, the oral applianceextends over occlusal surfaces of the teeth and/or over lingual surfacesof the teeth in need of treatment.

In various embodiments, oral appliances disclosed herein can bemanufactured to custom fit the patients' oral cavity as moreparticularly described below. Generally, a patient's mouth is firstscanned utilizing a digital data acquisition tool. The data obtained inthis manner can be used to form an initial digital record, the BI andthat image is retained in a database. A dental professional can alsoobtain an initial record of the patient's oral cavity by taking ananalog impression using alginate or other impression materials fromwhich the analog model or impression will be scanned thus yielding thesame BI. It is from this initial record of the patient's mouth, the BIthat future oral appliances can be made. This image can be used as apermanent record of the patient's mouth, which can then be digitallymanipulated yielding a three-dimensional representation of the tissuesto be analyzed through the platform carrier, Dig1, and for varioussensor and/or hydrogel locations, Dig2. The Dig2 can be the area thatthe sensors and/or hydrogel will be attached to the device and this caninclude cargo areas to hold the sensor. A virtual or real oralappliance, Dig3 is thereby formed by merging the additive digital image,Dig1, with the segmentally manipulated image, Dig2, to create the finaldetection image, Dig3. The Dig1 image merged with the Dig2 image createsthe Dig3 image from which the oral appliance can be created. The BIprovides an outline of at least a portion of and/or all the surfaces ofthe teeth, gingiva and/or other soft tissues, which a dentalpractitioner may wish to obtain information regarding. Other softtissues of the oral cavity include without limitations, the palate,muco-buccal and muco-labial tissues, floor of the mouth, tongue, buccaland labial mucosae, and any other oral tissues. An authorized user cangenerate Dig1 by using software to create a layer over the teeth andgingiva that tightly approximate these tissues. The original image isthen digitally enhanced to include a layer over the digital image.Digital image Dig1 resembles a virtual oral appliance, which can be usedto create a real oral appliance. Dig1 is the platform carrier from whichall future appliances will be based. With respect to Dig1, the BI of thepatient's teeth and gums, has not been manipulated or modified by thecomputer at this point, but has had a digitally represented overlay ofteeth and soft tissues. The additive process can be varied such that theoral appliance can be made thicker in some areas for stiffness andretention, such as over the teeth and thinner in other areas forflexibility and comfort, such as over the soft tissues. The platformcarrier can also vary chemically in different regions such that it mayhave a chemically stiffer polymer in one region and a more flexiblepolymer in another region. Alternatively, the edge of the platformcarrier can have a swellable hydrogel to press against the soft tissuesand thereby lock in the oral appliance and lock out the saliva, thuspreventing leakage out and leakage in. Other chemical or elasticformulations and permutations thereof can be mixed and matched to suit adesired result. The current analog model of manufacturing may not yieldthese variations.

In some embodiments, Dig1 comprises the virtual image of portions of theoral appliance. By using virtual three-dimensional (3D) imaging and 3Dprinting, one can utilize a gradient of physical and chemicalcharacteristics to modify the oral appliance. The printer can makeportions of the oral appliance thicker for stiffness or thinner forflexibility and comfort or include a cargo area for holding the sensor.These features may be programmable using a computer system. In someembodiments, the oral appliance can modulate materials in itscomposition to provide stiff or flexible variations while keeping theoral appliance at a uniform thickness.

The digital image is stored in a computer readable data storage mediumof a computer. Computer readable media, for example, store data that isaccessible by a computer, such as magnetic cassettes, flash memorycards, digital video disks, Bernoulli cartridges, random access memories(RAMs), read only memories (ROMs), and the like and may also be used inan exemplary operating environment. Computer readable media do notinclude signals.

Using computer software, an authorized user can generate a seconddigital image referred to as Dig2. The software generating Dig2 includespoints or discrete regions on the teeth and/or gingiva or other softtissues as boundaries corresponding to areas in the oral cavity that thedental practitioner may wish to diagnose. As used herein, the “gingivalmargin area” comprises an area within the oral cavity, which includesthe gum line and the attached gingiva, including the sulcus of the gums.The gingival margin area includes about 2 to 3 mm of tooth above the gumline. In some embodiments, the points or the discrete regions mayinclude buccal surfaces of the teeth, surrounding gingival tissue,occlusal surfaces of the teeth, lingual surfaces of the teeth, and/oradjacent gingival tissue on a lingual side of the teeth. Throughsoftware manipulation of the image of a patient's mouth, Dig2 can beadded or subtracted according to point boundaries to a predetermineddepth that corresponds to the desired thickness of the layer to bemerged with Dig1. For example, in some embodiments, Dig2 can have athickness layer of about 0.5 mm. This area is mapped out on the BI andan additive layer of 0.5 mm thickness is programmed onto the map. Thisis an additive or subtractive programming of three dimensional spacewhich is then merged precisely onto Dig1 in the exact area from which itwas virtually programmed. It is digital image Dig2, which contains thecargo area to hold the one or more sensors and/or hydrogel required todetect a selected pathology. Merging Dig1 with Dig2 creates the finalappliance Dig3.

FIG. 5 illustrates a virtual image of the polymer containing the one ormore sensors and/or hydrogel for the oral appliance. This illustratesthe additive or subtractive programming. In this case, the virtual 3Dimage 50 can be made by inputting data into the computer as to where theone or more sensors and/or hydrogel is to be disposed adjacent to thetreatment areas of the oral appliance. The computer system can generatethe interior surface 52 of the device where the one or more sensorsand/or hydrogel will be disposed in the polymer and be adjacent to thediagnostic area. The 3D image can be generated by adding or subtractingspace from the BI the soft and/or hard tissues to be monitored in aprecise pattern, yielding an image of the targeted area, Dig2, to bemerged with the original Dig1 platform device image. In someembodiments, the virtual 3D image 50 of the oral appliance will not havea floor to it as shown in the graph 55. This is because, in someembodiments, the 3D image generated will only have the discrete regionswhere the one or more sensors and/or hydrogel is to be disposed (Dig2).The remainder of the virtual image of the device can be constructedusing a spatial geometric pattern 54 that can be used to add the virtual3D image of the floor of the oral appliance and the exterior surface ofthe oral appliance. This includes height, width and depth to the virtualimage. By utilizing the Dig2 software, a monitoring system can becreated in which the one or more sensors and/or hydrogel can be appliedto targeted teeth and/or tissues in a precise three dimensional manner.By adding the dimension of depth to the vertical and lateral dimension,an oral appliance modeled upon Dig2 can apply one or more sensors and/orhydrogel in a third dimension. The above Dig2 image is a preciseaddition or subtraction of the targeted tissue accomplished throughcomputer programming, which is then saved to be used as furtherdescribed below.

Once digital image Dig1 and digital image Dig2 have been generated, theycan be merged via computer modeling to generate a third and finaldigital image, Dig3. In this manner, a virtual platform carrier oralappliance (Dig1) generated on the BI can be combined with a virtualdigital image of the treatment area generated based on Dig2, such thatthe Dig2 image is precisely merged onto the Dig1 platform appliance onthe inside of the Dig1 oral appliance to correspond to the exact areafrom which it was generated. As a result, Dig1 can be merged with anadditive or subtractive process Dig2 to create a final computer enhancedimage Dig3, which is a unique virtual three-dimensional image of theoral appliance including all or a portion of the oral appliance thatcontains one or more sensors and/or hydrogel in the areas adjacent tothe diagnostic areas of the oral cavity that are unique to a givenpatient.

In some embodiments, it is contemplated that only the surfaces of theteeth will be detected and not the gums or only the gums will bedetected.

Generating oral appliances that can provide three dimensional diagnosticassays can be used effectively for detecting and/or monitoring differentconditions of the oral cavity. In other embodiments, a bulge can beplaced on the exterior surface of the oral appliance that corresponds tothe lower jaw and the lingual aspect, which faces the floor of the mouthand the lingual veins. In this process, Dig1 is obtained as before,however, Dig2 is created through the additive process of creating abulge upon the exterior surface of Dig1. The bulge generated with Dig2can hold the one or more sensors and/or hydrogel to be applied to theoral cavity. Oral appliances having an external surface having a bulgecan be useful in detecting and/or monitoring many diseases and can assaysaliva from all areas of the mouth as well as pre-cancerous, cancerouscells and/or other markers from the mouth, lungs, trachea, esophagus,stomach, sinuses of other areas of the body.

In another aspect, a virtual oral appliance Dig3 can be generated, whichcan be used by a dental professional to treat halitosis. The tongue hasa rough surface due to the papillae on the tongue. This roughnesscreates millions of tiny spaces among the papillae that harbormicroorganisms which frequently cause halitosis. In this aspect, thepalate cover and the palatal aspects of the upper jaw form the externalsurface of the Dig1 virtual oral appliance. As a result, the Dig2virtual oral appliance can be generated by adding a roughened surfacethat is Velcro-like in texture, which would include one or more sensorsand/or hydrogel to detect volatile sulfur compounds produced by themicroorganisms harbored among papillae and which cause halitosis and candetect neoplastic cells or other organisms, bacterial or fungal forexample. A virtual Dig3 oral appliance generated based on the resultingmerger of Dig1 and Dig2 can be used as a scouring pad to assay thetongue and then formulate the proper treatment regimen to resolve thehalitosis. By closing the mouth and rubbing the tongue against thepalate and the teeth, a patient could physically “Pap smear” the tonguein a scraping and/or rubbing motion. The rough, scouring pad surface ofDig3 covering the upper jaw and palate (roof of the mouth) canphysically open and scrub the tiny spaces between papillae, therebyenabling increased sensitivity to detection of chemical, physical,and/or environmental parameters associated with halitosis. Simplescraping the tongue usually elicits a gag reflex. When one closes theirmouth and rubs their tongue against the roof of their mouth, there is nogag reflex, thus when rubbing the tongue to the palate with the abovedescribed oral appliance, one will physically scrape the tongue andcollect the material into the appliance which is then analyzed forproper treatment. FIG. 5A illustrates an enlarged view of a virtualimage (Dig2) of the regions along the sulcus (gumline) 56 where the oneor more sensors and/or hydrogel of the oral appliance will be loaded ina polymer gel material.

FIG. 5B illustrates an enlarged view of a virtual image (Dig1) of theoral appliance 59 that is made by taking a baseline digital image of theoral cavity and creating a digital image that corresponds to or layersover the oral cavity including the teeth, gums, soft tissue areas,and/or the palate. Dig1 does not have the virtual image of where the oneor more sensors and/or hydrogel is to be disposed. The lower portion ofthe virtual oral appliance corresponds to and will contact portions ofthe tongue and hard palate 58 as well as the soft palate 57.

FIG. 5C illustrates an enlarged view of a virtual image (Dig3) of theoral appliance. The virtual image is the merging of the Dig1 data andthe additive or subtractive data of Dig2, from which the oral appliancecan be produced that has regions along the sulcus (gumline) 63 where theone or more sensors and/or hydrogel of the oral appliance will be loadedin a polymer gel material. The lower portion of the virtual oralappliance corresponds to and will contact portions of the tongue andhard palate as well as the soft palate 65 and textured, palatal scouringpad 67 along each side of the oral cavity. It is from Dig 3 that theoral appliance can be manufactured.

By utilizing an oral appliance manufactured based on a virtual Dig3 oralappliance, the tongue of a patient can be assayed in part, forhalitosis, fungal or other infections, through rubbing, while theremaining portion of the oral appliance, both interior and exterioraspects of which can be used to detect chemical, physical, neoplasms,and/or environmental parameters from virtually every surface of the oralcavity in a long and sustained manner. In this embodiment, Dig2 canadditively or subtractively create a layer for the entire inside of theoral appliance and additively add a layer to the non-palatal portion ofthe upper oral appliance and the entire outer portion of the lower oralappliance. Both upper and lower oral appliances can apply one or moresensors and/or hydrogel to the entire mouth; inside and out. Held by theteeth and gum, the upper and lower oral appliances can apply one or moresensors and/or hydrogel through passive contact directly to the tissues.When one closes their mouth, there is no open space since the softtissues collapse against each other and the hard tissues, such that theupper and lower appliances contact all the tissues in a sustainedmanner. As a result, a complete assay of the entire soft tissues of themouth can be obtained to collect data of every hard and soft tissue.

In other aspects, tooth loss, gingival and bone grafting procedures,implants, and placement of regenerative tooth processes can also bemonitored by the methods described in this disclosure. In various otheraspects, the three dimensional methods described in this disclosure canbe useful to monitor other diseases or surgical procedures of the bodyas a whole.

In some embodiments, once the Dig3 virtual oral appliance is generatedin whatever iteration, a virtual 3D image is sent to be manufacturedusing conventional 3D printing, Carbon3D printing, hybrid manufacturingusing 3D printing along with conventional suck down manufacturing withrobotic insertions of sensors and/or hydrogels or other combinations ofinjection molding or other techniques. For example, in certainembodiments, the chemical composition for Dig1 portion can be stiffer inorder to better hold onto the teeth and gums and be devoid of absorptivequalities, while the Dig2 portion can be made of a different chemicalcomposition, which has absorptive qualities and can swell more easily.Useful chemical compositions comprise gels, hydrogels, polymer brushes,and other swellable chemicals. These can be mixed uniformly with one ormore sensors and/or hydrogel, or alternately infused into Dig2 materialafter printing of Dig3.

In some embodiments, the computer program uses an axis graph withphysical properties on one axis and chemical properties on the other.This data is used for manufacturing the device and, although holdingdifferent formulations will have chemical compatibility between them,such that when manufactured the formulations will seamlessly meldtogether as one piece, thus allowing the Dig3 oral appliance to befabricated without the use of adhesives, glues, or mechanical lockingdevices. In some embodiments, the one or more sensors and/or hydrogelcan be loaded and manufactured concurrently with the overall oralappliance. Alternatively, the sensor can be attached to the oralappliance by hand or machine. In some embodiments, the sensor can beattached to the interior and/or exterior of the device by an adhesive orthe sensors can be disposed in discrete regions of the oral appliance inthe cargo areas. In some embodiments, the sensor can have a soft polymerdisposed about it. The polymer is soft to prevent damage of the sensorand the surrounding gums. In some embodiments, the polymer can be anelectro conductive polymer that is disposed around or surrounds thesensor.

With this digital model, the oral appliance manufactured in accordancewith Dig 3 is now ready to be placed in the oral cavity of the patienteither in a wet or dry form. The hydrogel portion of the Dig3 oralappliance is contracted when dry and will expand when wetted. It is theDig2 portion of Dig3, which is the three-dimensional representation ofthe area to be detected which will monitor the diagnostic area in athree-dimensional manner once the oral appliance is inserted. Forembodiments in which the one or more polymers used to make the oralappliance include a hydrogel, the hydrogel of the Dig3 oral appliancecontinuously samples along a diffusion gradient. This phenomenon issimilar to a biologic wicking caused by the body tissues of the patient,which are at a lower diffusion gradient.

In various embodiments, the three-dimensional model has the hydrogelloaded and/or the sensor, the sensor web can be provided and the oralappliance can be made about the sensor, or sensor web.

Once the oral appliance is manufactured, the oral appliances are packedand shipped to a dental professional who will deliver them to thepatient with instructions for their use. The patient then performs asingle use assay and thereafter either downloads the information orsends the appliance to be analyzed. A new tray is used for each assayaccording to a prescribed regimen.

In some embodiments, oral appliances manufactured according to thethree-dimensional model described herein can also be utilized to monitorperiodontal or gum diseases. In gum disease the initial form of the gumsis often reddened and swollen. As such, the gums are larger than normal.As they heal, the gums shrink back to their normal, healed state sizeand become pink and firm. In order to generate a Dig2 system to treatgum diseases, Dig2 can be modified to take into account the anticipatedshrinking of the gums to insure that the detection layer is always inapposition to the diseased tissue. A sensor, for example a pressuresensor, can be positioned in the oral appliance adjacent this area andas the gums heal and shrink the pressure will decrease in this area. Insome embodiments, if the gums are swollen by 2 mm, there can be a twoweek or 14 oral appliance detection period. The first oral appliance foruse on the first day can have an initial Dig2 thickness of 0.6 mmidentified as Dig2A. The second oral appliance, identified as Dig2B, canhave a thickness of 0.7 mm and can be used by the patient on the secondday. On the third day, the patient can use Dig2C oral appliance, whichcan have a thickness of 0.8 mm. The process repeats itself until day 14when the thickness of Dig2N can be 2 mm, thus fully accounting for theshrinkage of the gums and also allowing the one or more sensors and/orhydrogel to always be in direct contact with the gums. If this approachwere not followed, it could result in the patient having a gap betweenDig2 and the gum and the resultant space would not allow for properassaying. This is a progressive system, in which the Dig3 oralappliances are manufactured to account for daily and/or weekly changesto the topography of changing soft tissues. Thus, in certainembodiments, the thickness of surface oral appliance is incrementallyconfigured for monitoring gum disease.

FIG. 6A schematically shows an embodiment of an oral appliance 200configured for application to the lower teeth and gums and a cargo area202 that has a pressure sensor 204 mounted either by hand or roboticallyon the exterior surface of the oral appliance, which for example, canmonitor pressure on a biting surface for teeth grinding (e.g., bruxism)and help in equilibrating a bite. The sensor will collect the data overa period of time. For example, over an evening period and the sensorwill measure the biting or grinding habits of the patient over theevening period.

In other embodiments, the Dig 3 oral appliance can be utilized as adiagnostic tool for testing of fluids in the oral cavity. In theseembodiments, the hydrogel of the Dig3 oral appliance is absorptive bothon its internal and external surfaces and can therefore be easily usedto test the gingival crevicular fluids and/or saliva present in the oralcavity for diagnostic purposes. After the patient wears the Dig3 oralappliance, the oral appliance can be removed, placed into a containerand then sent to a lab for analysis or in the case of sensors theinformation can be downloaded for analysis. The Dig3 oral appliance cantest oral fluids over longer periods of time, and is thus significantlymore effective than the fluid spot testing currently used in currenttechnology. In some embodiments, the oral appliance can includeabsorptive material that can retain the sample (e.g., cells, fluid(e.g., blood, saliva), etc.). Such material includes, but is not limitedto, absorptive hydrogels, absorptive sponge, or sponge-like material,polyvinyl acetate (PVA), polyurethane (PU), cellulose, polyester, rayon,cotton, and/or a combination thereof.

FIG. 6B schematically shows an embodiment of an oral appliance 206configured for application to the lower teeth and gums and a cargo area208 that has a hydrogel 210 disposed either by hand or robotically onthe interior surface of the oral appliance, which for example, cancollect cells, for example, from a cancerous site. The hydrogel can havea tab 212 for easy removal of the hydrogel, which can then be sent tothe lab for further testing. The hydrogel can be placed at discretepositions in the oral appliance to collect tissue samples, saliva,blood, bacteria or other material and then sent to the lab for analysis.

The dimensions of the oral appliance, among other things, will depend onthe target detection site. The oral appliance can be adapted to any sizeand shaped to receive at least a portion of the teeth and/or soft tissueareas inside the mouth. For example, the oral appliance is designed tocontour, support, and hold the polymer gel material and, in variousembodiments, extends to at least the muco-gingival junction, or at least2 mm to 5 mm buccally or lingually beyond a gingival margin, or contactall or substantially all of one or more teeth and/or soft tissue areasinside the mouth and adjacent buccal and lingual soft tissue areas.

In various embodiments, the oral appliance has a thickness of from about0.06 inches to about 0.2 inches, a depth of at least about 1 mm to about5 mm, and a width of from about 1 mm to about 10 mm. In certainembodiments, the thickness of the oral appliance is incrementallyconfigured for monitoring a gum disease.

Materials of Oral Appliance

The material of the oral appliance can be any material that can hold oneor more sensors and/or hydrogel or in some embodiments, retain a sample(e.g., blood, saliva, cells, etc.). In various embodiments, the materialfrom which the oral appliance can be manufactured includes swellablepolymer materials, such as, for example gels, hydrogels, polymer brushesor combinations thereof.

In various embodiments, polymer gels, hydrogels, and brush polymers canbe formulated to have varying degrees of swelling ability. Thus, atreatment that involves the application of pressure to soft tissues ofthe mouth can be accommodated through the specific formulation of Dig2materials to incorporate the desired amount or percentage of swellingduring treatment. In some embodiments, the polymer comprises 20 wt % to90 wt % of the formulation.

In various embodiments, the molecular weight of the gel can be varied asdesired. The choice of method to vary molecular weight is typicallydetermined by the composition of the gel (e.g., polymer, versusnon-polymer). For example, in various embodiments, when the gelcomprises one or more polymers, the degree of polymerization can becontrolled by varying the amount of polymer initiators (e.g., benzoylperoxide), organic solvents or activator (e.g., DMPT), crosslinkingagents, polymerization agent, incorporation of chain transfer or chaincapping agents and/or reaction time.

Suitable gel polymers may be soluble in an organic solvent. Thesolubility of a polymer in a solvent varies depending on thecrystallinity, hydrophobicity, hydrogen-bonding and molecular weight ofthe polymer. Lower molecular weight polymers will normally dissolve morereadily in an organic solvent than high-molecular weight polymers. Apolymeric gel that includes a high molecular weight polymer tends tocoagulate or solidify more quickly than a polymeric composition thatincludes a low-molecular weight polymer. Polymeric gel formulations thatinclude high molecular weight polymers also tend to have a highersolution viscosity than a polymeric gel that includes low-molecularweight polymers. In various embodiments, the molecular weight of thepolymer can be a wide range of values. The average molecular weight ofthe polymer can be from about 1000 to about 10,000,000; or about 1,000to about 1,000,000; or about 5,000 to about 500,000; or about 10,000 toabout 100,000; or about 20,000 to 50,000 g/mol.

In various embodiments, the gel has an inherent viscosity (abbreviatedas “I.V.” and units are in deciliters/gram), which is a measure of thegel's molecular weight and degradation time (e.g., a gel with a highinherent viscosity has a higher molecular weight and may have a longerdegradation time). Typically, when the polymers have similar componentsbut different molecular weights, a gel with a high molecular weightprovides a stronger matrix and the matrix takes more time to degrade. Incontrast, a gel with a low molecular weight degrades more quickly andprovides a softer matrix. In various embodiments, the gel has amolecular weight, as shown by the inherent viscosity, from about 0.10dL/g to about 1.2 dL/g or from about 0.10 dL/g to about 0.40 dL/g. OtherIV ranges include but are not limited to about 0.05 to about 0.15 dL/g,about 0.10 to about 0.20 dL/g, about 0.15 to about 0.25 dL/g, about 0.20to about 0.30 dL/g, about 0.25 to about 0.35 dL/g, about 0.30 to about0.35 dL/g, about 0.35 to about 0.45 dL/g, about 0.40 to about 0.45 dL/g,about 0.45 to about 0.55 dL/g, about 0.50 to about 0.70 dL/g, about 0.60to about 0.80 dL/g, about 0.70 to about 0.90 dL/g, about 0.80 to about1.00 dL/g, about 0.90 to about 1.10 dL/g, about 1.0 to about 1.2 dL/g,about 1.1 to about 1.3 dL/g, about 1.2 to about 1.4 dL/g, about 1.3 toabout 1.5 dL/g, about 1.4 to about 1.6 dL/g, about 1.5 to about 1.7dL/g, about 1.6 to about 1.8 dL/g, about 1.7 to about 1.9 dL/g, andabout 1.8 to about 2.1 dL/g.

In some embodiments, when the polymer materials have differentchemistries (e.g., high MW DLG 5050 and low MW DL), the high MW polymermay degrade faster than the low MW polymer.

In various embodiments, the gel can have a viscosity of about 300 toabout 5,000 centipoise (cp). In other embodiments, the gel can have aviscosity of from about 5 to about 300 cps, from about 10 cps to about50 cps, or from about 15 cps to about 75 cps at room temperature. Thegel may optionally have a viscosity enhancing agent such as, forexample, hydroxypropyl cellulose, hydroxypropyl methylcellulose,hydroxyethyl methylcellulose, carboxymethylcellulose and salts thereof,Carbopol, poly-(hydroxyethylmethacrylate),poly-(methoxyethylmethacrylate), poly(methoxyethoxyethyl methacrylate),polymethylmethacrylate (PMMA), methylmethacrylate (MMA), gelatin,polyvinyl alcohols, propylene glycol, mPEG, PEG 200, PEG 300, PEG 400,PEG 500, PEG 600, PEG 700, PEG 800, PEG 900, PEG 1000, PEG 1450, PEG3350, PEG 4500, PEG 8000 or combinations thereof.

In various embodiments, the gel is a hydrogel made of high molecularweight biocompatible elastomeric polymers of synthetic or naturalorigin. In other embodiments, the hydrogel material can hold collectedbiological materials when the hydrogel material is hypo-saturated,saturated, or supersaturated. There are many advantages resulting fromusing hydrogel in making the oral appliances described herein.Generally, hydrogel materials provide an effective contact medium forgum compression and for collecting biological materials for diagnosis.The above can hold the sample (e.g., saliva, blood, cells, etc.) whenthe oral appliance is removed and then the oral appliance can be sent tothe lab for testing. Sending out the entire oral appliance to the labcan prevent cross contamination of the patient's hands contaminating thesample collected by the hydrogel. In some embodiments, only the hydrogelcan be removed and then sent out to the lab for testing.

Hydrogels obtained from natural sources are particularly appealingbecause they are more likely to be biocompatible for in vivoapplications. Suitable hydrogels include natural hydrogels, such as forexample, gelatin, collagen, silk, elastin, fibrin andpolysaccharide-derived polymers like agarose, and chitosan, glucomannangel, hyaluronic acid, polysaccharides, such as cross-linkedcarboxyl-containing polysaccharides, or a combination thereof. Synthetichydrogels include, but are not limited to those formed from polyvinylalcohol, acrylamides such as polyacrylic acid andpoly(acrylonitrile-acrylic acid), polyurethanes, polyethylene glycol(for example, PEG 3350, PEG 4500, PEG 8000), silicone, polyolefins suchas polyisobutylene and polyisoprene, copolymers of silicone andpolyurethane, neoprene, nitrile, vulcanized rubber,poly(N-vinyl-2-pyrrolidone), acrylates such as poly(2-hydroxy ethylmethacrylate) and copolymers of acrylates with N-vinyl pyrolidone,N-vinyl lactams, polyacrylonitrile or combinations thereof. The hydrogelmaterials may further be cross-linked to provide further strength asneeded. Examples of different types of polyurethanes includethermoplastic or thermoset polyurethanes, aliphatic or aromaticpolyurethanes, polyetherurethane, polycarbonate-urethane or siliconepolyether-urethane, or a combination thereof.

In various embodiments, also useful material for preparing the oralappliances described in this disclosure comprise reactive segmentedblock copolymers containing hydrophilic domain(s) and showing goodsurface properties when the block copolymer is covalently bound tosubstrates containing complimentary functionality. The hydrophilicdomain(s) will comprise at least one hydrophilic monomer, such as, HEMA,glyceryl methacrylate, methacrylic acid (“MAA”), acrylic acid (“AA”),methacrylamide, acrylamide, N,N′-dimethylmethacrylamide, orN,N′-dimethylacrylamide; copolymers thereof; hydrophilic prepolymers,such as ethylenically unsaturated poly(alkylene oxide)s, cyclic lactamssuch as N-vinyl-2-pyrrolidone (“NVP”), or derivatives thereof. Stillfurther examples are the hydrophilic vinyl carbonate or vinyl carbamatemonomers. Hydrophilic monomers can be nonionic monomers, such as2-hydroxyethyl methacrylate (“HEMA”), 2-hydroxyethyl acrylate (“HEA”),2-(2-ethoxyethoxy)ethyl(meth)acrylate, glyceryl(meth)acrylate,poly(ethylene glycol(meth)acrylate), tetrahydrofurfuryl(meth)acrylate,(meth)acrylamide, N,N′-dimethylmethacrylamide,N,N′-dimethylacrylamide(“DMA”), N-vinyl-2-pyrrolidone (or other N-vinyllactams), N-vinyl acetamide, and combinations thereof. Still furtherexamples of hydrophilic monomers are the vinyl carbonate and vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277. Thecontents of these patents are incorporated herein by reference. Thehydrophilic monomer also can be an anionic monomer, such as2-methacryloyloxyethylsulfonate salts. Substituted anionic hydrophilicmonomers, such as from acrylic and methacrylic acid, can also beutilized wherein the substituted group can be removed by a facilechemical process.

The polymer gel material can comprise orally soluble or insolublepolymers. For example, the polymer gel material may be designed to beinsoluble in the oral environment, yet still release the medicament thatis coated on or internally imbedded in the polymer gel material. Variouspolymers whether soluble, insoluble, semi-soluble or combinations ofthese may be used to create a polymer gel material with specificactivities suitable for assaying. Many plastics and plastic combinationsare suitable for this application. A few examples of possible plasticsinclude: polyacrylates, polyamide-imide, phenolic, nylon, nitrileresins, petroleum resins, fluoropolymers, copolyvidones (copovidones),epoxy, melamine-formaldehyde, diallyl phthalate, acetal,coumarone-indene, acrylics, acrylonitrile-butadiene-styrene, alkyds,cellulosics, polybutylene, polycarbonate, polycaprolactones,polyethylene, polyimides, polyphenylene oxide, polypropylene,polystyrene, polyurethanes, polyvinyl acetates, polyvinyl chloride,poly(vinyl alcohol-co ethylene), styrene acrylonitrile, sulfonepolymers, saturated or unsaturated polyesters, urea-formaldehyde, or anylike plastics.

In one embodiment, the hydrogel material may comprise a backing material(e.g., a closed cell plastic backing material) to minimize collection ofthe biological material by the oral appliance. The hydrogel material canbe constructed to increase collection of the biological material toreceive a bolus collection or the polymer gel material may be designedto prevent biological material from spilling out of the hydrogelmaterial and allow the biological material to pass through the polymergel hydrogel over time to obtain a sustained collection profile. Inother words, in various embodiments, the hydrogel material may have aninternal structural spacing sized relative to the viscosity of thebiological material to absorb and allow the biological material to passtherethrough to achieve the desired collection profile, for example,immediate collection, bolus collection, and/or sustained or controlledcollection.

In some embodiments, the dimensions of the polymer material (e.g., gel,hydrogel, etc.), among other things, will depend on the target diagnosissite and whether local or systemic collection of the biological materialis required as well as the type of biological material collectionprofile to achieve. In some embodiments, the oral appliance is preparedprimarily of polymer material and can be adapted to any size and shaperequired to receive at least a portion of the teeth and/or soft tissueareas inside the mouth to collect the biological material. For example,the polymer material may, in various embodiments, extend to at least themuco-gingival junction, or at least 2 mm to 5 mm buccally or linguallybeyond a gingival margin, or contact all or substantially all of one ormore teeth and/or soft tissue areas inside the mouth and adjacent buccaland lingual soft tissue areas. In various embodiments, the polymermaterial contacts all or substantially all of one or more teeth and/orsoft tissue areas inside the mouth. In various embodiments, the polymermaterial contacts the soft tissue and teeth at or near a gingival marginor sulcus. In various embodiments, the polymer material has a thicknessof from about 0.06 inches to about 0.2 inches, a depth of at least about1 mm to about 5 mm and a width of from about 1 mm to about 10 mm.

Computer Implemented System

In various embodiments, the present disclosure provides a computerimplemented method of making an oral appliance. The method comprisescreating a digital record of a patient's oral cavity, the Base Image(BI), by obtaining a digital image of at least a portion of the teeth,and/or soft tissue of the oral cavity by using an imaging device. The BIis overlaid to create a first digital image, Dig1. Subsequently, asecond digital image, Dig2, comprising at least a portion of the teethand/or soft tissue of the oral cavity in need of a sensor is additivelyor subtractively generated. Thereafter, the first digital image, Dig1,and the second digital image, Dig2, are combined to form a third digitalimage, Dig3, of the oral cavity treatment area and the third digitalimage is then stored in the computer and used for manufacture.

In some embodiments, there is a computer implemented method of producingan oral appliance pre-loaded with at least one or more sensors and/orhydrogel using a computer, comprising: using the BI of the digital imageof the patient's mouth, generating first digital data representing anoverlay of at least a portion of the teeth and/or soft tissues areas ofthe oral cavity of a patient, generating second digital data byperforming a specified three dimensional addition of at least a portionof the teeth and/or soft tissues areas of the oral cavity to determinediscrete regions of the oral cavity in need of treatment, combining thefirst digital data and the second digital data to form third digitaldata, from which the oral appliance can be produced, wherein the thirddigital data comprises positions for at least one or more sensors and/orhydrogel to be placed at the discrete regions in the oral cavity in needof diagnosis.

In other embodiments, a computer-implemented method is provided fordiagnosing a condition of the teeth and/or soft tissue areas inside theoral cavity. The computer-implemented method comprises generating afirst digital data, Dig1, representing at least a portion of the teethand/or soft tissues areas of the oral cavity of a patient from the BI.Subsequently, a second digital data, Dig2, is generated by performingvia the computer a digital segmentation of at least a portion of theteeth and/or soft tissues areas of the oral cavity comprising discreteregions of the oral cavity in need of treatment. The first digital data,Dig1, and the second digital data, Dig2, are then combined via computerto form the third digital data, Dig3, from which the oral appliance canbe produced, wherein the oral appliance has at least one or more sensorsand/or hydrogel positioned at the discrete regions requiring diagnosisin the oral cavity.

In various embodiments, a computer based system further comprisescreating a virtual 3D image of the oral appliance indicating thediscrete regions requiring diagnosis in the oral cavity; displaying on adisplay the virtual 3D image and performing interactive diagnosis.Imaging devices utilized to generate the various digital data setsinclude, without limitations, a digital camera, X-ray device, hand-held3-D scanner, laser scanner, computerized tomography (CT) scanner,magnetic resonance imaging (MRI) scanner, coordinate measuring machine,destructive scanner or ultrasound scanner, generating first digitaldata, Dig1, representing at least a portion of the teeth and/or softtissues areas of the oral cavity of a patient based on an imaging deviceimage (BI), generating second digital data, Dig2, by performing via thecomputer a digital segmentation of at least a portion of the teethand/or soft tissues areas of the oral cavity comprising discrete regionsof the oral cavity in need of treatment, combining via the computer thefirst digital data, Dig1, and the second digital data, Dig2, to formthird digital data, Dig3, from which the oral appliance can be producedhaving at least one or more sensors and/or hydrogel positioned at thediscrete regions requiring diagnosis in the oral cavity.

In other embodiments, the three-dimensional representation of the thirddigital data, Dig3, is stored in a format suitable for use by amanufacturer to produce the oral appliance pre-loaded with at least oneor more sensors and/or hydrogel at areas targeted for diagnosis.Manufacturing comprises a first chemical composition according to thefirst digital data, Dig1, and a second chemical composition according tothe second digital data, Dig2. The two combined chemically merge andrepresent the image of the third digital data, Dig3. At least one of thechemical compositions includes one or more sensors and/or hydrogel whilethe other can be a polymer gel, brush polymer, another absorptivematerial or combinations thereof.

Referring to FIG. 7, it illustrates an embodiment of thecomputer-implemented system for producing an oral appliance. An inputdevice or scanner 60 is used to scan the oral cavity of and thusgenerate a digital record of the patient's mouth (BI). The scanner canbe an MRI scanner, a CT scanner, a PET scanner, a digital scanner, anX-Ray machine, or an intra-oral scanner, for example. In variousembodiments, scanner 60 can scan the patient's teeth, soft tissue, orboth to obtain a digital data set of the teeth and/or soft tissue areasinside the mouth from which is generated the BI. The digital data can bestored in a database, such as for example a computer that has aprocessor 62, which sends the digital data to its memory 64 and/or candisplay it in a virtual 3D image display 66 of processor 62. Thedatabase and/or processor can comprise an input device (e.g., keyboard,touch screen, voice activation, etc.) to allow a user to enter, display,edit, and/or transmit on or more images from Dig1, Dig2, Dig3. Theprocessor 62 comprises logic to execute one or more instructions tocarry instructions of the computer system (e.g., transmit instructionsto the 3D printer, etc.). The logic for executing instructions may beencoded in one or more tangible media for execution by the processor 62.For example, the processor 62 may execute codes stored in acomputer-readable medium such as memory 64. The computer-readable mediummay be, for example, electronic (e.g., RAM (random access memory), ROM(read-only memory), EPROM (erasable programmable read-only memory)),magnetic, optical (e.g., CD (compact disc), DVD (digital video disc)),electromagnetic, semiconductor technology, or any other suitable medium.

Based on memory 64, processor 62 can generate Dig2 and Dig3 andthereafter send a 3D image to the 3D printer 68 of a stereolithographyapparatus.

In various embodiments, an authorized user can input, edit data andapprove or prescribe a treatment plan based on the virtual 3D imagesdisplayed at the user interface of the computer processor 62 and/oranother treating computer networked with computer processor 62. Althoughthe components of the system of FIG. 7 are shown as separate, they maybe combined in one or more computer systems. Indeed, they may be one ormore hardware, software, or hybrid components residing in (ordistributed among) one or more local or remote computer systems. It alsoshould be readily apparent that the components of the system asdescribed herein may be merely logical constructs or routines that areimplemented as physical components combined or further separated into avariety of different components, sharing different resources (includingprocessing units, memory, clock devices, software routines, logiccommands, etc.) as required for the particular implementation of theembodiments disclosed. Indeed, even a single general purpose computer(or other processor-controlled device) executing a program stored on anarticle of manufacture (e.g., recording medium or other memory units) toproduce the functionality referred to herein may be utilized toimplement the illustrated embodiments. It also will be understood that aplurality of computers or servers can be used to allow the system to bea network based system having a plurality of computers linked to eachother over the network or Internet or the plurality of computers can beconnected to each other to transmit, edit, and receive data via cloudcomputers.

The computer (e.g., memory, processor, storage component, etc.) may beaccessed by authorized users. Authorized users may include at least onedentist or dental specialist, dental hygienist, oral surgeon, physician,surgeon, nurse, patient, and/or health care provider, manufacturer,etc.).

The user can interface with the computer via a user interface that mayinclude one or more display devices (e.g., CRT, LCD, or other knowndisplays) or other output devices (e.g., printer, etc.), and one or moreinput devices (e.g., keyboard, mouse, stylus, touch screen interface, orother known input mechanisms) for facilitating interaction of a userwith the system via user interface. The user interface may be directlycoupled to database or directly coupled to a network server system viathe Internet or cloud computing. In accordance with one embodiment, oneor more user interfaces are provided as part of (or in conjunction with)the illustrated systems to permit users to interact with the systems.

The user interface device may be implemented as a graphical userinterface (GUI) containing a display or the like, or may be a link toother user input/output devices known in the art. Individual ones of aplurality of devices (e.g., network/stand-alone computers, personaldigital assistants (PDAs), WebTV (or other Internet-only) terminals,set-top boxes, cellular/phones, screenphones, pagers, blackberry, smartphones, iPhone, iPad, table, peer/non-peer technologies, kiosks, orother known (wired or wireless) communication devices, etc.) maysimilarly be used to execute one or more computer programs (e.g.,universal Internet browser programs, dedicated interface programs, etc.)to allow users to interface with the systems in the manner described.Database hardware and software can be developed for access by usersthrough personal computers, mainframes, and other processor-baseddevices. Users may access and data stored locally on hard drives,CD-ROMs, stored on network storage devices through a local area network,or stored on remote database systems through one or more disparatenetwork paths (e.g., the Internet).

The database can be stored in storage devices or systems (e.g., RandomAccess Memory (RAM), Read Only Memory (ROM), hard disk drive (HDD),floppy drive, zip drive, compact disk-ROM, DVD, bubble memory, flashdrive, redundant array of independent disks (RAID), network accessiblestorage (NAS) systems, storage area network (SAN) systems, etc.), CAS(content addressed storage) may also be one or more memory devicesembedded within a CPU, or shared with one or more of the othercomponents, and may be deployed locally or remotely relative to one ormore components interacting with the memory or one or more modules. Thedatabase may include data storage device, a collection component forcollecting information from users or other computers into centralizeddatabase, a tracking component for tracking information received andentered, a search component to search information in the database orother databases, a receiving component to receive a specific query froma user interface, and an accessing component to access centralizeddatabase. The receiving component is programmed for receiving a specificquery from one of a plurality of users. The database may also include aprocessing component for searching and processing received queriesagainst data storage device containing a variety of informationcollected by collection device.

The disclosed system may, in some embodiments, be a computer networkbased system. The computer network may take any wired/wireless form ofknown connective technology (e.g., corporate or individual LAN,enterprise WAN, intranet, Internet, Virtual Private Network (VPN),combinations of network systems, etc.) to allow a server to providelocal/remote information and control data to/from other locations (e.g.,other remote database servers, remote databases, network servers/userinterfaces, etc.). In accordance with one embodiment, a network servermay be serving one or more users over a collection of remote anddisparate networks (e.g., Internet, intranet, VPN, cable, specialhigh-speed ISDN lines, etc.). The network may comprise one or moreinterfaces (e.g., cards, adapters, ports) for receiving data,transmitting data to other network devices, and forwarding received datato internal components of the system (e.g., 3D printers, printer heads,etc.).

In accordance with one embodiment of the present application, the datamay be downloaded in one or more textual/graphical formats (e.g., RTF,PDF, TIFF, JPEG, STL, XML, XDFL, TXT etc.), or set for alternativedelivery to one or more specified locations (e.g., via e-mail, fax,regular mail, courier, etc.) in any desired format (e.g., print, storageon electronic media and/or computer readable storage media such asCD-ROM, etc.). The user may view viewing the search results andunderlying documents at the user interface, which allows viewing of oneor more documents on the same display.

In various embodiments, the computer software can create a 2D or 3Ddigital image of the patient's oral cavity to allow the treatmentprovider to review and discuss the proposed treatment with the patient.In another embodiment, the software can process the scanned data andprovide the user/operator with useful data including tooth measurements(e.g. arch width, arch length, tooth size, angulations, sulcus size,etc.) to assist the user in fine-tuning the assay plan. The computer canthen provide the operator with options in staging the assay plan fromone stage to another stage, or it can completely generate all stagesranging from the initial to final desired stage. The staging can be doneautomatically.

FIG. 8 is a flow chart illustrating the logic steps followed byprocessor 62 of FIG. 7. The first step 70 comprises generating a BaseImage (BI) of at least a portion of the teeth and/or soft tissues byusing an imaging device. In step 72, the BI is stored in the memory ofthe processor. In step 74, a first data set (Dig1) is generated by thecomputer layering over the BI of at least a portion of the teeth and/orsoft tissues. The Dig1 is stored.

In step 76, a second data set (Dig2) is generated by digitally adding aspecific three dimensional layer over at least a portion of the teethand/or soft tissues from the Base Image.

Thereafter, in step 78, the processor can decide if all discrete regionsof the oral cavity in need of assay have been identified or if they havenot been, then the digital segmentation step will occur again. Dig2 willalso be checked for accuracy.

If all the desired discrete regions have been identified, then in step80, the processor stores the data, which includes the discrete regionsin need of assay as a separate set corresponding to Dig2. The first andsecond data sets are combined in step 82 to generate a third data setcorresponding to Dig3. The third data set is stored in step 84 and thensent to a 3D printer in step 86.

FIG. 9A is a flow chart illustrating an embodiment of thecomputer-implemented system for assaying a patient utilizing an oralappliance produced according to this disclosure. As described above, theoral cavity of the patient is scanned or a mold can be scanned in step90. Based on the information gathered in step 90, Dig1 is generated instep 92. Subsequently, a second digital data set is generated and Dig2is obtained in step 94. As discussed above, Dig1 and Dig2 digital datasets are combined, in particular Dig2 is subtracted from Dig2, in step96 to generate Dig3, which provides the logic and instructions tomanufacture Dig3 in step 98. A group of steps 118, i.e., steps 92through 98, is optionally replaced by operations detailed below inaccordance with the group of steps 119 shown in FIG. 9B with relation tofurther embodiments of the present disclosure.

FIG. 9B is a flow chart illustrating an embodiment of thecomputer-implemented system for assaying a patient utilizing an oralappliance produced according to this disclosure. Based on theinformation gathered in step 90, Dig1 is generated in step 93.Subsequently, a second digital data set is generated and Dig2 isobtained in step 95. As discussed above, Dig1 and Dig2 digital data setsare combined, and in this particular embodiment Dig2 is added to Dig1,in step 97 to generate Dig3, which provides the logic and instructionsto manufacture Dig3 in step 99.

Following step 98 the oral appliances produced by a stereolithography,or extrusion type 3D printing, are then rinsed and loaded with one ormore sensors in step 100. The oral appliances are then dried and packedin step 102 and shipped to a dental professional in step 104.Alternatively, there may be no rinse step or sensors and/or hydrogelloading as the stereolithography machine may have the one or moresensors and/or hydrogel may have already been loaded. In step 106, thepatient receives the oral appliances and inserts them as required in adaily process in step 108. After the monitoring period of step 110 iscompleted, each oral appliance is removed and analyzed in step 112 orthe hydrogel insert is removed by the patient and the hydrogel is sentto the laboratory for analysis. Alternatively, if a diagnosis needs tobe made, the oral appliances can be sent to a laboratory for testing andthen the oral appliances disposed of by the laboratory.

Stereolithography

Stereolithography is the manufacturing process that may be employed forrapidly and accurately producing the oral appliances described herein. Acommercially-available stereolithography apparatus (SLA) may be employedto carry out the rapid prototyping methods described herein. In manycases, stereolithography is carried out using a defined amount of liquidUV-curable photopolymer, which can be a “resin” and an ultraviolet (UV)laser to assemble all or a portion of the oral appliance one layer at atime. According to such methods, the laser beam will “trace” across-sectional pattern, for each layer of the oral appliance, on thesurface of the liquid resin. By exposing the resin to UV energy, theresin solidifies (or “cures”) in accordance with the pattern traced bythe beam of energy, which adheres to the layer beneath it.

After a pattern has been traced by the beam of UV energy, a so-calledelevator platform within the SLA descends by a single layer thickness,typically about 0.05 mm to 0.15. Next, a resin-filled blade traversesacross each part of the cross-section, which re-coats the model with newUV-curable resin. On this new layer of resin, the subsequent layerpattern is traced, adhering to the previous layer. This process allowsfor a complete three-dimensional, real-sized prototyped oral applianceto be produced. After a prototype oral appliance is produced, the oralappliance may, optionally, be cleaned and the excess resin removedtherefrom by immersion in a chemical bath and then cured in a UV oven.U.S. Pat. No. 4,575,330 (“Apparatus for Production of Three-DimensionalObjects by Stereolithography”) provides a non-limiting method ofstereolithography, which may be used in the present application and ishereby incorporated by reference in its entirety. With respect to theoral appliance described herein, the print heads of the SLA can dispensepolymers according to instructions provided by Dig1 and Dig2 to generateDig3 as described above. Accordingly, the viscosity of the polymer,curing rates, feed rates to the print heads can be considered inmanufacturing the oral appliances described herein.

An alternate method of stereolithography involves the deposition ofsuccessive layers of liquid or powder onto a hard surface, with eachlayer immediately cured by a beam of UV energy, and in this way buildsup the oral appliance from a series of cross sectional patterns of Dig3.These layers, which correspond to the virtual cross section of Dig3, arejoined together or fused automatically to create the oral appliance.Further, it will be apparent to those skilled in the art that variousmodifications and variations can be made to various embodimentsdescribed herein without departing from the spirit or scope of theteachings herein. Thus, it is intended that various embodiments coverother modifications and variations of various embodiments within thescope of the present teachings.

Control System, Apparatus and Method

A further embodiment of the present disclosure varies the aforesaidembodiments to effect design and construction of an oral appliance whichis directed to improved diagnostic area dynamics. Unless otherwisestated, this embodiment incorporates the features discussed above exceptas further modified herein. In particular, the base image (BI)previously discussed is used to construct an oral appliance which is tobe used to monitor areas in the oral cavity with control of contactpressure applied to a diagnostic area, which includes any or all ofteeth and tissues discussed above, and/or areas surrounding thetreatment area.

Any of the various forming techniques discussed above are optionallyused to manufacture the oral appliance. Forming techniques for the oralappliance may be categorized into three groups. Extrusion type 3Dprinting wherein print heads successively extrude layers of meltedmaterials to produce the oral appliance. Alternatively, instead of usingmelted material, UV curable materials may be used wherein print headseject the UV curable materials which once ejected are exposed to UV rayswhich cure them in place. Similarly, materials may be ejected which arecured by other means such as exposure to oxygen or infrared rays.Depending on the characteristics of the materials to be used, e.g., somematerials may not be suitable for thermoforming wherein they are meltedand allowed to solidify. Extrusion type 3D printing will be hereinafterconsidered to apply to types of printing wherein a material is ejectedand subsequently cured by any method. Photopolymerization 3D printing,also termed stereolithography (SLA) as discussed above, is a processwherein a vat of liquid polymer which is cured by exposure light isacted upon by light rays to cure selected portions of the liquidpolymer, photopolymer, in successive layers to form the oral appliance.Recent developments in photopolymerization 3D printing have resulted inthe use of graphene materials which provide a very rigid structure,e.g., a structure having a high modulus of elasticity. Graphene materialis optionally used in any embodiments described herein where such astructural characteristic is required or desirable.

It is noted that in the above discussion the term “stereolithography”has been occasionally applied herein to both photopolymerization methodswherein an object is produced using a vat of liquid polymer andextrusion type 3D printing because it generally it relates a method ofproducing 3D objects. As will be appreciated by those skilled in theart, where multiple print heads and materials are involved, the abovediscussion is relating extrusion type 3D printing.

Additionally, a vacuum forming hybrid method is optionally used whereina carrier is formed from a sheet of thermoformable material by vacuummolding the sheet over a 3D model of the base image BI or a modifiedversion thereof as will be discussed below. Further materials are addedto the formed sheet using any or all of 3D printing, robotic applicationof material, or immersion in a solution containing hydrogel.

Referring to FIG. 10A, a cross section of an oral appliance 130 formedof a platform carrier shell 120, which includes a data collection device302 (e.g., sensor) that monitors physical, chemical, biological, and/orenvironmental information associated with the oral cavity, is shown. Thedata collection device (e.g., sensor) is disposed in a cargo area 303,which is a space in the oral appliance that corresponds to the virtualimage of Dig2 and is added onto or subtracted from the virtual image ofDig1 and made in the device when it is manufactured using virtual imageDig3. In some embodiments, the oral appliance can be printed usingCarbon3D technology by operation parameters for the continuousproduction of the oral appliance using 3D printing technology asdescribed in US Publication No. 20150097315 having Ser. No. 14/569,202filed Dec. 12, 2014. The entire disclosure of this patent publication isherein incorporated by reference into the present disclosure. In someembodiments, the cargo area 303 can be filled with an electroconductivemedical polymer 301 that includes microparticles and/or nanoparticles asdiscussed below that conduct electricity to and from the sensor.

The view of the oral appliance 130 in FIG. 10A corresponds to a view ofthe oral appliance taken along line IXa-IXa of the oral appliance 10 ofFIG. 1. The carrier shell 120 is illustrated disposed on the upper tooth16 and associated tissue 150 (e.g., gingival tissue) of a patient inorder to show that the carrier shell tightly conforms to the underlyingoral structure. For the purpose of simplicity, the associated tissue 150is shown as homogeneous. However, it is to be understood that theassociated tissue 150 may include both soft tissue, e.g., gums, andbone, and the extent of the oral appliance 130 is not to be consideredlimited to such coverage of the structure of the oral cavity. Adiagnostic area 160 of the associated tissue 150 is shown which is inneed of monitoring. The diagnostic area, for example, can be gingivalcells where cancerous cells were removed or it may be an area ofperiodontal disease that requires monitoring of saliva in which thesaliva will weakly conduct electricity to the sensor. If there is toolittle saliva or bacteria increase in the area, this may interfere withthe conduction of the electricity to the sensor and it will send asignal to the processor external to the oral appliance, where it will bestored and an alert will be generated to the wearer and/or the healthcare provider as the conductivity will be too low. The data collectiondevice 302 is disposed in a cargo area 303 adjacent to the teeth andcontacts the soft tissue of the oral cavity in this embodiment.

In some embodiments, the sensor is configured to detect any suitablemarker or trigger in the saliva, mucosal fluids, crevicular fluids orair of the oral cavity. The trigger may be a negative or positiveindicator of oral hygiene or oral conditions. Examples of suitablemarkers/triggers include pH, molecules, proteins, organisms, oralactivities such as triclosan, or the like. More specifically, suitablemarkers include phosphates, amino acids, potassium salts, or stannoussalts. In some embodiments, the sensor is configured to detect aparticular pH or range of pH.

In some embodiments, the sensor can be a pH sensor taking intraoral pHand plaque pH. It is known that acidic fermentation products produced byplaque microorganisms in the presence of sugar and carbohydrates arestrongly associated with dental caries. Because of the importance ofplaque pH, measurement of plaque pH is now widely accepted as a methodof evaluating the effect of carbohydrates on oral health. In someembodiments, caries is indicated by low saliva pH, local pH (e.g., atspecific locations on the hard tissue) and by acid-producing oralbacteria (specifically Lactobacillus species, Streptococcus mutans, andActinomyces species), where the sensor can detect such low pH.

In some embodiments, the oral conditions identified by the devicesdescribed herein include, but are not limited to, conditions associatedwith poor oral care, conditions which may be diagnosed by examination ofthe oral cavity, and systemic conditions which have been recognized orotherwise identified by the American Dental Association to be correlatedwith poor oral care.

Oral diseases suitable for detection include caries, gingivitis,periodontitis, halitosis, fungal infections and dry mouth. Gingivitismay be indicated by the markers IL-1β, PGE2, arginine and Gingipains.Gingivitis may also be indicated by elevated levels of one or more of P.gingivalis, C. gingivalis, P. melaminogenica, Treponema denticola,Bacterioides forsythus and S. mitis. Halitosis may be indicated byvolatile sulfur compounds, including methyl mercaptan, dimethylsulfideand hydrogen sulfide. Periodontitis may be indicated by elastases,dipeptidylpeptidase, β-glucuronidase, lactoferrin, platelet-activatingfactor (PAF), ICPT (pyridinoline cross-linked carboxyterminaltelopeptide), cathepsin B (a cysteine protease), cystatins, MMP-1,collagenase-2 (matrix metalloproteinase, MMP-8), MMP-13 (collagenase-3),gelatinase (MMP-9), hydroxyl-deoxyguanosine and immunoglobulins such asIgA, IgG and IgM. Bone-related biomarkers from oral fluids associatedwith periodontal diseases also include calprotectin, osteocalcin,ostenocetin and osteopontin.

Caries may be indicated by low saliva pH, local pH (e.g., at specificlocations on the hard tissue) and by acid-producing oral bacteria(specifically Lactobacillus species, Streptococcus mutans, andActinomyces species). A few non-oral based systemic diseases that arealso indicative with oral malodor are: fetor hepaticus, an example of arare type of bad breath caused by chronic liver failure; upper and lowerrespiratory tract infections utilizing phlegm and sputum (sinus,bronchial and lung infections); renal infections and renal failure; andtrimethylaminuria (“fish odor syndrome”) (Tangerman A. Halitosis inmedicine: a review. Int Dent J. 2002 June; 52 Suppl. 3:201-6), which isincorporated by reference herein in its entirety. High concentrations ofacetone (known as “acetone breath”) in breath can indicate diabeticketoacidosis.

In some embodiments, the pH sensor can detect unwanted levels from toothwhitening compositions. For example, the pH of different whiteningproducts ranges from 3.67 (highly acidic) to 11.13 (highly basic). Thedentist-supervised home-bleaching products have a mean pH of 6.48 (range5.66 to 7.35). The over-the-counter whitening products have a mean pH of8.22 (range 5.09 to 11.13), and the whitening toothpastes have a mean pHof 6.83 (range 4.22 to 8.35). The pH sensor can detect these ranges andranges above or below these ranges. This will cause the system to recordthe pH data and if a range is reached that is above or below the setrange, the system will send an alert notifying the user or healthcarepractitioner. In this way, the oral appliance can monitor the deliveryof medicaments (e.g., drugs, bleaching products, etc.) to the oralcavity.

FIG. 10B shows the platform carrier shell 120 absent the tooth andassociated tissue 150. The platform carrier 120 corresponds to thevirtual oral appliance defined by the digital image Dig1, whichcorresponds to a substantially uniform layer disposed over the baseimage BI so as to conform to the oral structure. Hence, theoretically,when the platform carrier 120 is situated as shown in FIG. 10A, thepressure exerted on the diagnostic area is negligible as no deflectionof the platform carrier 120 is needed to fit on the underlying oralcavity structure. In many situations this is desirable as the diagnosticarea 160 may be highly sensitive to pressure. Additionally, such aconfiguration is desirable when there are no specific diagnostic areasand the platform carrier is provided with the apparatus 300 to begenerally disposed in the oral cavity. In such instances, the platformcarrier 130 is formed of any of the aforesaid materials that aresuitable for harboring the apparatus 300. In this case, the oralappliance 130 is formed by any of extrusion 3D printing,photopolymerization 3D printing, vacuum forming over a 3D printed moldof the oral cavity formed using the base image BI, a combination of anyor all of these techniques, and/or the like.

As noted above, the oral appliance 130 may be used to apply theapparatus 300, which may include one or more sensors and/or hydrogel,and exert negligible pressure to the underlying oral cavity structure.However, there are situations wherein enhanced contact with certainregions of the oral cavity structure is desirable. As would be expectedof the substantially contact pressureless fit of the oral appliance 130,motion of the jaw and tongue can result in the oral appliance losingcontact at areas of the oral cavity structure, which will result in lossof the intimate contact of the one or more sensors and/or hydrogel inthe oral appliance 130 with an area of intended diagnosis, such as thediagnostic area 160 and a resultant loss of transferal of theinformation from the area to be diagnosed. Furthermore, loss of contactwith the underlying oral structure allows saliva or ingested beveragesto circulate between the oral appliance and the area to be diagnosedresulting in some of the information to be lost and/or corrupted. Thus,in some situations it is desirable to modify the oral appliance 130 toincrease contact pressure with the area to be diagnosed in order tomaintain contact with the diagnostic area. Additionally, it may also bedesirable to increase contact pressure with areas surrounding the areato be diagnosed in order to better exclude liquids, such as saliva orbeverages, from the surface of the oral appliance 130 in contact withthe area to be diagnosed. The data collection device 302 is disposed ina cargo area 303 adjacent to the teeth and contacts the soft tissue ofthe oral cavity in this embodiment.

FIG. 10C is a top plan view of the oral appliance of FIG. 1 depicted ina simplified manner lacking intricate detail for simplicity of viewing,indicating various components of the apparatus that monitors physical,chemical, biological, and/or environmental information associated withthe oral cavity (dashed line outlined) disposed at the bottom ofpositions for alignment adjacent bottoms of top molars, sensorspositioned in indentations of the interior surface of the oral appliancefor measurements of properties adjacent teeth, and sensors positioned inindentations of the exterior surface of the oral appliance. For example,the data collection device 302 (e.g., sensor) can measure oxygen orcarbon dioxide content in the oral cavity to monitor conditions such as,for example, sleep apnea, where oxygen content will be low. Thus, thesensor can be placed in the air flow of the oral cavity and measure theuser's respiration rate, especially if the user is breathing very hardthrough the mouth and if the respiration rate is low an alert will begenerated. This is a major advance from a patient wearing a bulky anduncomfortable C-Pap machine or other large intra-oral anti-snoringdevices.

Multiplex Sensor

In some embodiments, the oral appliance includes multiplex or aplurality of sensors including temperature sensors, activation sensors,motion sensors, positional sensors, force sensors, radiation sensors,pressure sensors, atmospheric pressure sensors, pulse oximeterscapnographs, airflow sensors, alcohol breathalyzers, and/or salivasensors. Accordingly, user monitoring system and related biometric dataprocessing methods allows the multiplexing of sensors and dataprocessing.

Pressure sensors can detect if the user is biting down with a sufficientamount of force to ensure proper placement of the oral appliance therebyensuring optimal protection of the user's jaw and teeth. One or morepressure sensors can be used to determine whether dental appliance isappropriately positioned for taking accurate biometric and/orenvironmental data.

One or more of these sensors, e.g., pressure sensor(s), and/or motion(force) sensor(s), can also be used to detect usage and non-usage forthe purpose of system activation and system power conservation. Forexample, if the oral appliance has been removed, the inactivityindication can be used to trigger a low-power or sleep-mode, therebyextending the life of the power source.

FIG. 10D is a top plan view of the carrier shell of FIG. 1, which hasmultiplex sensors, which is shown in a simplified manner lackingintricate detail for simplicity of viewing, indicating one or morecomponents of the oral appliance, such as a data collection device orsensor 302 disposed in the interior of the oral appliance, interfacedevice 304, power supply 306, and processing device 308 (dashed lineoutlined), disposed at bottom of positions for alignment adjacentbottoms of top molars, positioned in indentations of the interiorsurface of the oral appliance for measurements of properties adjacentteeth, and positioned in indentations of the exterior surface of theoral appliance for measurements of physical, chemical, biological,and/or environmental information associated with the oral cavity.

FIG. 10E is a top plan view of the oral appliance of FIG. 1 depicted ina simplified manner lacking intricate detail for simplicity of viewing,indicating various components of the apparatus that monitors physical,chemical, biological, and/or environmental information associated withthe oral cavity. In this view, a sensor web 305 is provided in theinterior of the device that allows contact with the teeth and cancollect data on one or more parameters occurring in the oral cavity.This sensor web can include temperature sensors, activation sensors,motion sensors, positional sensors, force sensors, radiation sensors,pressure sensors, atmospheric pressure sensors, pulse oximeterscapnographs, airflow sensors, alcohol breathalyzers, and/or salivasensors. In some embodiments, the sensor web extends longitudinally inthe oral appliance and continuously with the biting surface of theteeth.

FIG. 1OF is a top plan view of the oral appliance of FIG. 1 depicted ina simplified manner lacking intricate detail for simplicity of viewing,indicating various components of the apparatus that monitors physical,chemical, biological, and/or environmental information associated withthe oral cavity. In this view, a plurality of data collection devicesare disposed in the interior surface and exterior surface of the oralappliance and there is an electroconductive medical polymer 307 disposedthroughout the interior of the oral appliance. The data collectiondevice or sensor 302 is disposed in the interior of the oral appliance,interface device 304, power supply 306, and processing device 308(dashed line outlined) are disposed on the exterior of the oralappliance.

In some embodiments, the electroconductive medical polymer 307 cancomprise PermaStat PLUS™ available in acrylic, acrylonitrile butadienestyrene (ABS), polycarbonate/acrylonitrile-butadiene-styrene terpolymerblend (PC/ABS), acetyl, polycarbonate, polyolefins such as polypropylene(PP) and polyethylene (PE) and other resin systems (RTP Company, Winona,Minn.), polymers rendered electrically conductive, such as acetals suchas polyoxymethylene (POM), acrylics such as poly(methyl methacrylate)(PMMA), fluoropolymers such as polytetrafluoroethylene (PTFE),polyvinylidene difluoride (PVDF) and perfluoroalkoxy alkanes (PFA),polycarbonate (PC) and PC alloys, polyethereketone (PEEK), polyolefins(PP), (PE), and polymethylpentene (PMP), polysulfone (PSU),polyethersulfone (PES), thermoplastic polyurethane elastomer (TPUR), andstyrenics polystyrene (PS) and ABS. In some embodiments, the polymercomprises polypyrrole (PPy), polyaniline (PANI),poly(3,4-ethylenedioxythiophene) (PEDT, PEDOT), polythiophene (PTh),polythiophene-vinylene (PTh-V), poly(2,5-thienylenevinylene) (PTV),poly(3-alkylthiophene) (PAT), poly(p-phenylene) (PPP),poly-p-phenylene-sulphide (PPS), poly(p-phenylenevinylene) (PPV),poly(p-phenylene-terephthalamide) (PPTA), polyacetylene (PAc),poly(isothianaphthene) (PITN), poly(a-naphthylamine) (PNA), polyazulene(PAZ), polyfuran (PFu), polyisoprene (PIP), polybutadiene (PBD), andpoly(3-octylthiophnene-3-methylthiophene) (POTMT). Suitableelectroconductive polymers that can be used in the device are availablefrom Liquidia Technologies, Inc. and are described in U.S. Pat. No.8,685,461. This entire disclosure is herein incorporated by referenceinto the present disclosure. These electroconductive polymers be inmicroparticle or nanoparticle form and can enhance sensing to and fromthe data collection device (e.g., sensor, sensor web, sensor array,etc.) by enhancing electrical conduction to and from the data collectiondevice.

Hydrogels

In some embodiments, suitable resins include photocurable hydrogels likepoly(ethylene glycols) (PEG) and gelatins. PEG hydrogels have been usedto deliver a variety of biological materials, including Growth factors;however, a great challenge facing PEG hydrogels crosslinked by chaingrowth polymerizations is the potential for irreversible protein damage.Conditions to maximize release of the biologicals from photopolymerizedPEG diacrylate hydrogels can be enhanced by inclusion of affinitybinding peptide sequences in the monomer resin solutions, prior tophotopolymerization allowing sustained delivery. Gelatin is a biopolymerfrequently used in food, cosmetic, pharmaceutical and photographicindustries. It is obtained by thermal denaturation or chemical andphysical degradation of collagen. There are three kinds of gelatin,including those found in animals, fish and humans. Gelatin from the skinof cold water fish is considered safe to use in pharmaceuticalapplications. UV or visible light can be used to crosslink appropriatelymodified gelatin.

Three-dimensional oral appliances produced by the methods and processesof the present application may be final, finished or substantiallyfinished products, or may be intermediate products subject to furthermanufacturing steps such as surface treatment, laser cutting, electricdischarge machining, etc. Intermediate products include products forwhich further additive manufacturing, in the same or a differentapparatus, may be carried out. For example, a fault or cleavage line maybe introduced deliberately into an ongoing “build” by disrupting, andthen reinstating, the gradient of polymerization zone, to terminate oneregion of the finished product, or simply because a particular region ofthe finished product or “build” is less fragile than others.

Numerous different oral appliances can be made by the methods andapparatus of the present application, including custom fit oralappliances that correspond to the digital scan taken from the patient'smouth as discussed above.

In some embodiments, the oral appliance has at least one, or a pluralityof, pores or channels formed therein. The processes described herein canproduce oral appliances with a variety of different properties. Hence insome embodiments the oral appliances are rigid; in other embodiments theproducts are flexible or resilient. In some embodiments, the oralappliances are a solid; in other embodiments, the oral appliances are agel such as a hydrogel or have layers of such. In some embodiments, theoral appliances have a shape memory (that is, return substantially to aprevious shape after being deformed, so long as they are not deformed tothe point of structural failure). In some embodiments, the oralappliances are unitary (that is, formed of a single polymerizableliquid); in some embodiments, the products are composites (that is,formed of two or more different polymerizable liquids). Particularproperties will be determined by factors such as the choice ofpolymerizable liquid(s) employed.

FIG. 11 is a block diagram of a system in which the oral appliance isused to monitor, collect, transfer, process, and store physical,chemical, biological, and/or environmental information obtained from theoral cavity. The apparatus 300 is applied to a user and wirelesslytransfers the information to, for example, a router 310, personalcomputer 312, phone 314, and/or any other electronic device capable ofperforming wireless transfers of the information. The router 310,personal computer 312, and/or phone 314 can then further transfer thisdata to and/or from the router 310, personal computer 312, phone 314,and/or network 316 using wired and/or wireless techniques. Thisinformation may be further processed and/or stored via the network 316by using, for example, the personal computer 312, server 318, and/ordatabase 320. Each of the router 310, phone 314, personal computer 312,network 316 may include capability to receive and/or transmitinformation from and/or to any other device using wired and/or wirelesstechniques and/or protocols, such as but not limited to, Bluetooth,Wi-Fi, radio frequency, optical, and/or any other type of wirelesscommunication linkage. The network 312 may be any type of networkincluding, but not limited to, a wide area network, local area network,and/or telephone network.

FIG. 12 is a block diagram of the oral appliance. The oral applianceincludes a data collection device 302, interface device 304, processingdevice 308, and power supply 306 operatively coupled together usingunidirectional and/or bidirectional connections. The data collectiondevice 302 includes one or more sensors designed to monitor physical,chemical, biological, and/or environmental information associated withthe oral cavity, and provide this information to the processing device308 and/or interface device 304. The processing device 308 may performfurther processing on the information obtained from the data collectiondevice 302, and provide the processed information to the interfacedevice 304. The interface device 304 is able to wirelessly transfer databetween the oral appliance and devices external to the oral appliance,such as the router 310, phone 314, and personal computer 312, andnetwork 316 shown in FIG. 11. The power supply 306 provides power to thedata collection device 302, interface device 304, and processing device308.

The oral appliance may also include a computer-readable storage device(not shown) operatively coupled to at least one of the data collectiondevice, processing device, and/or interface device. Thecomputer-readable storage device is configured to store data provided bythe data collection device 302, interface device 304, and/or processingdevice 308 for subsequent retrieval and/or transmission. Thecomputer-readable storage device may include, for example, Flash memory,RAM, ROM, EEPROM, or any other computer-readable storage medium whichcan be used to store information.

FIG. 13 is a flowchart illustrating an embodiment of a method inaccordance with the disclosure. Information is monitored by the datacollection device in the oral cavity in step 322, and the monitoredinformation is optionally processed by the processing device in step324. The optionally processed information is transferred by theinterface device in step 326, and the transferred information isreceived by one or more devices external to the oral appliance in step328. The received information is processed by one or more devicesexternal to the oral appliance in step 330, and the processedinformation is then stored for future access in step 332.

FIG. 14 is a flowchart illustrating another embodiment of a method inaccordance with the disclosure. Information is sampled using a samplingmedium, such as hydrogel or other absorptive materials, in the oralcavity in step 334, and the sampling medium is removed from the oralappliance in step 336. The sampling medium is processed to obtaininformation associated with the oral cavity in step 338, and theinformation is processed by one or more devices external to the oralappliance in step 340. The processed information is then stored forfuture access in step 342.

Accordingly, the embodiments disclosed herein may take the form of anentirely hardware embodiment, an entirely software embodiment (includingfirmware, resident software, micro-code, and the like) or an embodimentcombining software and hardware aspects that may all generally bereferred to herein as a “circuit,” “module”, or “system.” Further, atleast a portion of these embodiments may take the form of a computerprogram product embodied in one or more computer readable medium(s)having computer readable program code embodied thereon.

One or more embodiments, or elements thereof, can be implemented in theform of an apparatus including a storage device or memory and at leastone processing device or processor that is coupled to the memory andoperative to perform a method according to one or more embodiments.

One or more embodiments disclosed herein, or a portion thereof, make useof software running on a general purpose computer or workstation. By wayof example only and without limitation, FIG. 15 is a block diagram of anembodiment of a machine in the form of a computing system 400, withinwhich is a set of instructions 402 that, when executed, cause themachine to perform any one or more of the methodologies according to thedisclosed embodiments. In one or more embodiments, the machine operatesas a standalone device; in one or more other embodiments, the machine isconnected (e.g., via a network 422) to other machines. In a networkedimplementation, the machine operates in the capacity of a server or aclient user machine in a server-client user network environment.Exemplary implementations of the machine, as contemplated by embodimentsdisclosed herein, include but are not limited to, a server computer,client user computer, personal computer (PC), tablet PC, personaldigital assistant (PDA), cellular telephone, mobile device, palmtopcomputer, laptop computer, desktop computer, communication device,personal trusted device, web appliance, network router, switch orbridge, or any machine capable of executing a set of instructions(sequential or otherwise) that specify actions to be taken by thatmachine.

The computing system 400 includes a processing device(s) 404 (e.g., acentral processing unit (CPU), a graphics processing unit (GPU), orboth), program memory device(s) 406, and data memory device(s) 408,which communicate with each other via a bus 410. The computing system400 further includes display device(s) 412 (e.g., liquid crystalsdisplay (LCD), flat panel, solid state display, or cathode ray tube(CRT)). The computing system 400 includes input device(s) 414 (e.g., akeyboard), cursor control device(s) 416 (e.g., a mouse), disk driveunit(s) 418, signal generation device(s) 420 (e.g., a speaker or remotecontrol), and network interface device(s) 424, operatively coupledtogether, and/or with other functional blocks, via bus 410.

The disk drive unit(s) 418 includes machine-readable medium(s) 426, onwhich is stored one or more sets of instructions 402 (e.g., software)embodying any one or more of the methodologies or functions herein,including those methods illustrated herein. The instructions 402 mayalso reside, completely or at least partially, within the program memorydevice(s) 406, the data memory device(s) 408, and/or the processingdevice(s) 404 during execution thereof by the computing system 400. Theprogram memory device(s) 406 and the processing device(s) 404 alsoconstitute machine-readable media. Dedicated hardware implementations,such as but not limited to ASICs (Application Specific IntegratedCircuits), programmable logic arrays, and other hardware devices canlikewise be constructed to implement methods described herein.Applications that include the apparatus and systems of variousembodiments broadly comprise a variety of electronic and computersystems. Some embodiments implement functions in two or more specificinterconnected hardware modules or devices with related control and datasignals communicated between and through the modules, or as portions ofan ASIC. Thus, the example system is applicable to software, firmware,and/or hardware implementations.

The term “processing device” as used herein is intended to include anyprocessor, such as, for example, one that includes a CPU (centralprocessing unit) and/or other forms of processing circuitry. Further,the term “processing device” may refer to more than one individualprocessor. The term “memory” is intended to include memory associatedwith a processor or CPU, such as, for example, RAM (random accessmemory), ROM (read only memory), a fixed memory device (for example,hard drive), a removable memory device (for example, diskette), a flashmemory and the like. In addition, the display device(s) 412, inputdevice(s) 414, cursor control device(s) 416, signal generation device(s)420, etc., can be collectively referred to as an “input/outputinterface,” and is intended to include one or more mechanisms forinputting data to the processing device(s) 404, and one or moremechanisms for providing results associated with the processingdevice(s). Input/output or I/O devices including but not limited tokeyboards (e.g., alpha-numeric input device(s) 414, display device(s)412, and the like) can be coupled to the system either directly (such asvia bus 410) or through intervening input/output controllers (omittedfor clarity).

In an integrated circuit implementation of one or more embodiments ofthe disclosure, multiple identical die are typically fabricated in arepeated pattern on a surface of a semiconductor wafer. Each such diemay include a device described herein, and may include other structuresand/or circuits. The individual dies are cut or diced from the wafer,then packaged as integrated circuits. One skilled in the art would knowhow to dice wafers and package die to produce integrated circuits. Anyof the exemplary circuits or method illustrated in the accompanyingfigures, or portions thereof, may be part of an integrated circuit.Integrated circuits so manufactured are considered part of thisspecification.

An integrated circuit in accordance with the embodiments of thedisclosed embodiments can be employed in essentially any applicationand/or electronic system in which buffers are utilized. Suitable systemsfor implementing one or more embodiments of the disclosed embodimentsinclude, but are not limited, to personal computers, interface devices(e.g., interface networks, high-speed memory interfaces (e.g., DDR3,DDR4), etc.), data storage systems (e.g., RAID system), data servers,etc. Systems incorporating such integrated circuits are considered partof the disclosed embodiments. Given the teachings provided herein, oneof ordinary skill in the art will be able to contemplate otherimplementations and applications.

In accordance with various embodiments, the methods, functions or logicdescribed herein are implemented as one or more software programsrunning on a computer processor. Dedicated hardware implementationsincluding, but not limited to, application specific integrated circuits,programmable logic arrays and other hardware devices can likewise beconstructed to implement the methods described herein. Further,alternative software implementations including, but not limited to,distributed processing or component/object distributed processing,parallel processing, or virtual machine processing can also beconstructed to implement the methods, functions or logic describedherein.

The embodiment contemplates a machine-readable medium orcomputer-readable medium containing instructions 302, or that whichreceives and executes instructions 302 from a propagated signal so thata device connected to a network environment 322 can send or receivevoice, video or data, and to communicate over the network 322 using theinstructions 302. The instructions 302 are further transmitted orreceived over the network 322 via the network interface device(s) 324.The machine-readable medium also contains a data structure for storingdata useful in providing a functional relationship between the data anda machine or computer in an illustrative embodiment of the systems andmethods herein.

While the machine-readable medium 302 is shown in an example embodimentto be a single medium, the term “machine-readable medium” should betaken to include a single medium or multiple media (e.g., a centralizedor distributed database, and/or associated caches and servers) thatstore the one or more sets of instructions. The term “machine- readablemedium” shall also be taken to include any medium that is capable ofstoring, encoding, or carrying a set of instructions for execution bythe machine and that cause the machine to perform anyone or more of themethodologies of the embodiment. The term “machine-readable medium”shall accordingly be taken to include, but not be limited to:solid-state memory (e.g., solid-state drive (SSD), flash memory, etc.);read-only memory (ROM), or other non-volatile memory; random accessmemory (RAM), or other re-writable (volatile) memory; magneto-optical oroptical medium, such as a disk or tape; and/or a digital file attachmentto e-mail or other self-contained information archive or set of archivesis considered a distribution medium equivalent to a tangible storagemedium. Accordingly, the embodiment is considered to include anyone ormore of a tangible machine-readable medium or a tangible distributionmedium, as listed herein and including art-recognized equivalents andsuccessor media, in which the software implementations herein arestored.

It should also be noted that software, which implements the methods,functions and/or logic herein, are optionally stored on a tangiblestorage medium, such as: a magnetic medium, such as a disk or tape; amagneto-optical or optical medium, such as a disk; or a solid statemedium, such as a memory card or other package that houses one or moreread-only (non-volatile) memories, random access memories, or otherre-writable (volatile) memories. A digital file attachment to e-mail orother self-contained information archive or set of archives isconsidered a distribution medium equivalent to a tangible storagemedium. Accordingly, the disclosure is considered to include a tangiblestorage medium or distribution medium as listed herein and otherequivalents and successor media, in which the software implementationsherein are stored.

As previously stated, although the specification describes componentsand functions implemented in accordance with embodiments of thedisclosure with reference to particular standards and protocols, theembodiments are not limited to such standards and protocols.

The illustrations of embodiments of the disclosure described herein areintended to provide a general understanding of the structure of variousembodiments, and they are not intended to serve as a completedescription of all the elements and features of apparatus and systemsthat might make use of the structures described herein. Many otherembodiments will become apparent to those skilled in the art given theteachings herein; other embodiments are utilized and derived therefrom,such that structural and logical substitutions and changes can be madewithout departing from the scope of this disclosure. The drawings arealso merely representational and are not drawn to scale. Accordingly,the specification and drawings are to be regarded in an illustrativerather than a restrictive sense.

Embodiments are referred to herein, individually and/or collectively, bythe term “embodiment” merely for convenience and without intending tolimit the scope of this application to any single embodiment or conceptif more than one is, in fact, shown. Thus, although specific embodimentshave been illustrated and described herein, it should be understood thatan arrangement achieving the same purpose can be substituted for thespecific embodiment(s) shown; that is, this disclosure is intended tocover any and all adaptations or variations of various embodiments.Combinations of the above embodiments, and other embodiments notspecifically described herein, will become apparent to those of skill inthe art given the teachings herein.

In the foregoing description of the embodiments, various features aregrouped together in a single embodiment for the purpose of streamliningthe disclosure. This method of disclosure is not to be interpreted asreflecting that the claimed embodiments have more features than areexpressly recited in each claim. Rather, as the following claimsreflect, disclosed subject matter lies in less than all features of asingle embodiment. Thus the following claims are hereby incorporatedinto the Detailed Description, with each claim standing on its own as aseparate example embodiment.

Given the teachings of the disclosure provided herein, one of ordinaryskill in the art will be able to contemplate other implementations andapplications of the techniques of the disclosure. Although illustrativeembodiments of the disclosure have been described herein with referenceto the accompanying drawings, it is to be understood that the disclosureis not limited to those precise embodiments, and that various otherchanges and modifications are made therein by one skilled in the artwithout departing from the scope of the appended claims.

While particular embodiments of the present disclosure have been shownand described, it will be appreciated by those skilled in the art that,based upon the teachings herein, changes and modifications may be madewithout departing from this disclosure and its broader aspects and,therefore, the appended claims are to encompass within their scope allsuch changes and modifications as are within the true spirit and scopeof this disclosure. The true spirit and scope is considered to encompassdevices and processes, unless specifically limited to distinguish fromknown subject matter, which provide equivalent functions as required forinteraction with other elements of the claims and the scope is notconsidered limited to devices and functions currently in existence wherefuture developments may supplant usage of currently available devicesand processes yet provide the functioning required for interaction withother claim elements. Furthermore, it is to be understood that thedisclosure is solely defined by the appended claims.

1.-3. (canceled)
 4. A computer implemented method of producing an oralappliance containing a discrete region for placing a sensor to collectbiological information about a patient's oral cavity, the computerimplemented method comprising: generating first digital datarepresenting at least a portion of teeth and/or soft tissue areas of theoral cavity of the patient, the first digital data generated from animaging device having a base image of the oral cavity; and generatingsecond digital data from the base image by performing an additive layerof at least a portion of the teeth and/or soft tissues areas of the oralcavity to determine the discrete region of the oral cavity to place thesensor, combining the first digital data (Dig1) and the second digitaldata (Dig2) to form third digital data (Dig3) from which the oralappliance can be produced into 3D printing data, wherein the thirddigital data comprises the discrete region for placing the sensor tocollect the biological information of the patient's oral cavity.
 5. Acomputer implemented method of claim 4, wherein the method furthercomprises operating a manufacturing system to produce the oral applianceincluding the discrete region for placing the sensor.
 6. A computerimplemented method of claim 4, wherein the region for placing the sensorcomprises a cargo area configured to house the sensor.
 7. A computerimplemented method of claim 4, wherein the third digital data (Dig3) isformed by one of (i) subtracting the second digital data (Dig2) from thefirst digital data (Dig1) or (ii) adding the second digital data (Dig2)to the first digital data (Dig1).
 8. A computer system for making anoral appliance containing a discrete region for placing a sensor tocollect biological information about a patient's oral cavity, thecomputer system comprising logic encoded in the computer for generatinga first digital data (Dig1) representing at least a portion of teethand/or soft tissue areas of the oral cavity of the patient, the firstdigital data is layered onto a Base Image recorded by an imaging device;logic encoded in the computer for generating a second digital data(Dig2) by performing an additive layer of at least a portion of theteeth and/or soft tissue areas of the oral cavity to determine thediscrete region of the oral cavity to place the sensor; logic encoded inthe computer for combining the first digital data and the second digitaldata to form a third digital data (Dig3) from which the oral appliancecan be produced, wherein the third digital data comprises the discreteregion for placing the sensor to collect the biological information ofthe patient's oral cavity.
 9. A computer system for making an oralappliance according to claim 8, further comprising logic encoded in thecomputer to initiate a manufacturing sequence to manufacture the oralappliance from the third digital data.
 10. A computer system for makingan oral appliance according to claim 8, wherein the third digital data(Dig3) is formed by one of (i) subtracting the second digital data(Dig2) from the first digital data (Dig1) or (ii) adding the seconddigital data (Dig2) to the first digital data (Dig1). 11.-21. (canceled)22. A computer-readable medium for making an oral appliance containing adiscrete region for placing a sensor to collect biological informationabout a patient's oral cavity, the computer-readable medium comprisinginstructions that, when executed by a processing device, cause thecomputer to: generate first digital data representing at least a portionof teeth and/or soft tissue areas of the oral cavity of the patient, thefirst digital data generated from an imaging device having a base imageof the oral cavity; generate a second digital data from the base imageby performing an additive layering of at least a portion of the teethand/or soft tissue areas of the oral cavity to determine the discreteregion of the oral cavity to place the sensor; and combine the firstdigital data (Dig1) and the second digital data (Dig2) to form a thirddigital data (Dig3) from which an oral appliance can be produced into 3Dprinting data, wherein the third digital data comprises the discreteregion for placing the sensor to collect the biological information ofthe patient's oral cavity
 23. A computer-readable medium comprisinginstructions that, when executed by a processing device, performoperations comprising: monitoring information associated with an oralcavity from a data collection device of a three-dimensional oralappliance; the data collection device having at least one sensorconfigured to sense the information associated with the oral cavity; andan interface device cooperatively coupled to the data collection device,the interface device configured to transfer the information from thesensor device to a receiving device external to the oral cavity or thedevice itself is removed and sent for analysis.
 24. A computer-readablemedium of claim 23, wherein the information comprises at least one ofpH, temperature, pressure, O2 content, CO2 content, and bacterialcontent.
 25. A computer-readable medium of claim 23, wherein theoperations further comprise monitoring, using the data collectiondevice, at least one of continuously and periodically.
 26. Acomputer-readable medium of claim 23, wherein the operations furthercomprise transferring, using the interface device, the informationexternal to the oral appliance wirelessly.
 27. A computer-readablemedium of claim 23, wherein the operations further comprise: processing,using the processing device, the information associated with the oralcavity; and transferring, using the processing device, the processedinformation to the interface device.
 28. A computer-readable medium ofclaim 22, wherein the operations further comprise forming the thirddigital data (Dig3) by one of (i) subtracting the second digital data(Dig2) from the first digital data (Dig1) or (ii) adding the seconddigital data (Dig2) to the first digital data (Dig1).
 29. An oralappliance for collecting biological information about at least a portionof teeth and/or soft tissue areas inside an oral cavity, the oralappliance comprising an interior surface having a sampling mediumdisposed in or on at least a portion of and/or all of the interiorsurface of the oral appliance, the interior surface being formed to fitcontours of at least the portion of the teeth and/or soft tissue areasinside the oral cavity and being configured for holding the samplingmedium in contact with at least the portion of the teeth and/or softtissue areas inside the oral cavity, the sampling medium configured tocollect biological tissue from the oral cavity and be removed from theinterior surface of the oral appliance.
 30. An oral appliance accordingto claim 29, wherein the sampling medium comprises a hydrogel, and thedevice itself is then analyzed.
 31. An oral appliance according to claim29, wherein the sampling medium is disposed at a discrete location inthe oral appliance and is configured to wick biological tissue from theoral cavity, which is disposed adjacent to the sampling medium.
 32. Anoral appliance according to claim 29, wherein the sampling medium isfurther configured to collect biological fluids, exudates or cells.